Author: "Jean Fontan" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Jean Fontan"' showing total 62 results

Start Over Author "Jean Fontan"

62 results on '"Jean Fontan"'

1. Prognostic impact of translocation t(14;16) in multiple myeloma according to the presence of additional genetic lesions

Author: Anaïs Schavgoulidze, Aurore Perrot, Titouan Cazaubiel, Xavier Leleu, Lydia Montes, Caroline Jacquet, Karim Belhadj, Sabine Brechignac, Laurent Frenzel, Thomas Chalopin, Philippe Rey, Jean-Marc Schiano de Collela, Mamoun Dib, Denis Caillot, Margaret Macro, Jean Fontan, Laure Buisson, Luka Pavageau, Murielle Roussel, Salomon Manier, Mohamad Mohty, Ludovic Martinet, Hervé Avet-Loiseau, and Jill Corre
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2023
Full Text: View/download PDF

2. Long-term analysis of the RiBVD phase II trial reveals the unfavorable impact of TP53 mutations and hypoalbuminemia in older adults with mantle cell lymphoma; for the LYSA group

Author: Sylvain Carras, Alexia Torroja, Anouk Emadali, Emilie Montaut, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Emmanuelle Tchernonog, Anna Schmitt, Roch Houot, Caroline Dartigeas, Sarah Barbieux, Selim Corm, Anne Banos, Ludovic Fouillet, Jehan Dupuis, Margaret Macro, Joel Fleury, Fabrice Jardin, Clementine Sarkozy, Ghandi Damaj, Pierre Feugier, Luc Matthieu Fornecker, Cecile Chabrot, Veronique Dorvaux, Krimo Bouabdallah, Sandy Amorim, Reda Garidi, Laurent Voillat, Bertrand Joly, Nadine Morineau, Marie Pierre Moles, Hacene Zerazhi, Jean Fontan, Yazid Arkam, Magda Alexis, Vincent Delwail, Jean Pierre Vilque, Loic Ysebaert, Barbara Burroni, Mary Callanan, Steven Le Gouill, and Rémy Gressin
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Between 2011 and 2012, a phase II trial evaluated the use of the RiBVD (rituximab, bendamustine, velcade and dexamethasone) combination as first-line treatment for mantle cell lymphoma (MCL) patients over the age of 65. We have now re-examined the classic prognostic factors, adding an assessment of TP53 mutation status. Patients (N=74; median age 73 years) were treated with the RiBVD combination. Median progression-free survival (mPFS) was 79 months and median overall survival (mOS) was 111 months. TP53 mutation status was available for 54/74 (73%) patients. TP53 mutations (TP53mt) were found in 12 patients (22.2%). In multivariate analysis, among the prognostic factors (PF) evaluated, only TP53mt and an albumin level (Alb) 3.6 g/dL were independently associated with a shorter mPFS. A hazard ratio (HR) of 3.16 (1.3-9.9, P=0.014) was obtained for TP53mt versus TP53 wild-type (wt), and 3.6 (1.39-9.5, P=0.009) for Alb
Published: 2023
Full Text: View/download PDF

3. Immune Thrombocytopenia Revealing Enriched IgG-4 Peri-Renal Rosai-Dorfman Disease Successfully Treated with Rituximab: A Case Report and Literature Review.

Author: Jerome Razanamahery, Sebastien Humbert, Jean-Francois Emile, Fleur Cohen-Aubart, Jean Fontan, Philippe Maksud, Sylvain Audia, and Julien Haroche
Subjects: immune thrombocytopenia, histiocytosis, Rosai Dorfman disease, Erdheim Chester disease, rituximab, Medicine (General), R5-920
Abstract: Immune thrombocytopenia (ITP) is a rare autoimmune-mediated condition characterized by isolated thrombocytopenia (
Published: 2021
Full Text: View/download PDF

4. Early relapse after autologous transplant for myeloma is associated with poor survival regardless of cytogenetic risk

Author: Jill Corre, Lydia Montes, Elodie Martin, Aurore Perrot, Denis Caillot, Xavier Leleu, Karim Belhadj, Thierry Facon, Cyrille Hulin, Mohamad Mohty, Jean Fontan, Margaret Macro, Sabine Brechignac, Arnaud Jaccard, Anne-Marie Stoppa, Frederique Orsini-Piocelle, Didier Adiko, Laurent Voillat, Faiza Keddar, Marly Barry, Helene Demarquette, Marie-Noelle Certain, Isabelle Plantier, Murielle Roussel, Benjamin Hébraud, Thomas Filleron, Michel Attal, and Hervé Avet-Loiseau
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2020
Full Text: View/download PDF

5. A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma

Author: Rémy Gressin, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Sylvain Carras, Emmanuelle Tchernonog, Anna Schmitt, Roch Houot, Caroline Dartigeas, Jean Michel Pignon, Selim Corm, Anne Banos, Christiane Mounier, Jehan Dupuis, Margaret Macro, Joel Fleury, Fabrice Jardin, Clementine Sarkozy, Ghandi Damaj, Pierre Feugier, Luc Matthieu Fornecker, Cecile Chabrot, Veronique Dorvaux, Krimo Bouadallah, Sandy Amorin, Reda Garidi, Laurent Voillat, Bertrand Joly, Philippe Solal Celigny, Nadine Morineau, Marie Pierre Moles, Hacene Zerazhi, Jean Fontan, Yazid Arkam, Magda Alexis, Vincent Delwail, Jean Pierre Vilque, Loic Ysebaert, Steven Le Gouill, Mary B. Callanan, and for the Lymphoma Study Association
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (P
Published: 2019
Full Text: View/download PDF

6. Upfront autologous stem cell transplantation for newly diagnosed elderly multiple myeloma patients: a prospective multicenter study

Author: Laurent Garderet, Eric Beohou, Denis Caillot, Anne Marie Stoppa, Cyrille Touzeau, Marie Lorraine Chretien, Lionel Karlin, Philippe Moreau, Jean Fontan, Didier Blaise, Emmanuelle Polge, Mor Seny Gueye, Souhila Ikhlef, Zora Marjanovic, Myriam Labopin, and Mohamad Mohty
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: The feasibility and efficacy of high-dose melphalan followed by autologous hematopoietic stem cell transplantation in newly diagnosed elderly patients with multiple myeloma was analyzed prospectively. Fifty-six multiple myeloma patients, aged 65 years or over, from 6 French centers were studied. The induction therapy was bortezomib-based in combination with dexamethasone and either thalidomide, cyclophosphamide or lenalidomide, for 4–6 cycles. Peripheral blood stem cells were collected after high-dose cyclophosphamide plus G-CSF or G-CSF alone, with plerixafor if needed. The conditioning regimen consisted of melphalan at 140 mg/m2 in 18 patients (36%) and 200 mg/m2 in 32 (64%). Three months post autologous hematopoietic stem cell transplantation, a 2-month consolidation phase with either lenalidomide plus dexamethasone or bortezomib-based combination therapy was allowed, but maintenance treatment was not given. All but 6 patients underwent autologous hematopoietic stem cell transplantation and 3 had tandem transplantations. The treatment-related mortality was 0% at 100 days post transplantation. Sixty-eight percent received consolidation therapy following transplantation. The best response achieved was 40% complete response, 36% very good partial response, and 18% partial response. After a median follow up of 21 months (range 6–31), the estimated progression-free and overall survival rates at two years were 76% [95%CI: (61.6–94.1)] and 88% [95%CI: (76.7–100)], respectively. The higher dose of melphalan (200 mg/m2) afforded superior progression-free and overall survival rates. This prospective study provides evidence for the safety and efficacy of autologous hematopoietic stem cell transplantation as a first-line treatment approach in elderly multiple myeloma patients. (clinicaltrials.gov identifier: 01671826)
Published: 2016
Full Text: View/download PDF

7. Phase II study of bendamustine, bortezomib and dexamethasone as second-line treatment for elderly patients with multiple myeloma: the Intergroupe Francophone du Myelome 2009-01 trial

Author: Philippe Rodon, Cyrille Hulin, Brigitte Pegourie, Mourad Tiab, Bruno Anglaret, Lotfi Benboubker, Henry Jardel, Olivier Decaux, Brigitte Kolb, Murielle Roussel, Laurent Garderet, Xavier Leleu, Olivier Fitoussi, Carine Chaleteix, Philippe Casassus, Pascal Lenain, Bruno Royer, Anne Banos, Riad Benramdane, Pascale Cony-Makhoul, Mamoun Dib, Jean Fontan, Anne-Marie Stoppa, Catherine Traullé, Jean-Pierre Vilque, Marie-Odile Pétillon, Claire Mathiot, Thomas Dejoie, Hervé Avet-Loiseau, and Philippe Moreau
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2015
Full Text: View/download PDF

8. Biallelic deletion of 1p32 defines ultra-high-risk myeloma, but monoallelic del(1p32) remains a strong prognostic factor

Author: Anaïs Schavgoulidze, Alexis Talbot, Aurore Perrot, Titouan Cazaubiel, Xavier Leleu, Salomon Manier, Laure Buisson, Sabrina Mahéo, Laura Do Souto Ferreira, Luka Pavageau, Cyrille Hulin, Jean-Pierre Marolleau, Laurent Voillat, Karim Belhadj, Marion Divoux, Borhane Slama, Sabine Brechignac, Margaret Macro, Anne-Marie Stoppa, Laurence Sanhes, Frédérique Orsini-Piocelle, Jean Fontan, Marie-Lorraine Chretien, Hélène Demarquette, Mohamad Mohty, Hervé Avet-Loiseau, and Jill Corre
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Abstract: Cytogenetic abnormalities (CAs) are known to be the preponderant prognostic factor in multiple myeloma. Our team has recently developed a prognostic score based on 6 CAs, with which del(1p32) appears to be the second worst abnormality after del(17p). This study aimed to confirm the adverse effect of 1p32 deletion in patients with newly diagnosed multiple myeloma (NDMM). Among 2551 patients with newly diagnosed multiple myeloma, 11% were harboring del(1p32). Their overall survival (OS) was significantly inferior compared with patients without del(1p32) (median OS: 49 months vs 124 months). Likewise, progression-free survival was significantly shorter. More importantly, biallelic del(1p32) conferred a dramatically poorer prognosis than a monoallelic del(1p32) (median OS: 25 months vs 60 months). As expected, the OS of patients with del(1p32) significantly decreased when this abnormality was associated with other high-risk CAs [del(17p), t(4;14), or gain(1q)]. In the multivariate analysis, del(1p32) appeared as a negative prognostic factor; after adjustment for age and treatment, the risk of progression was 1.3 times higher among patients harboring del(1p32), and the risk of death was 1.9 times higher. At the dawn of risk-adapted treatment strategies, we have confirmed the adverse effect of del(1p32) in multiple myeloma and the relevance of its assessment at diagnosis.
Published: 2023

9. Combining thrombopoietin receptor agonists with immunosuppressive drugs in adult patients with multirefractory immune thrombocytopenia, an update on the French experience

Author: Etienne Crickx, Mikael Ebbo, Etienne Rivière, Odile Souchaud‐Debouverie, Louis Terriou, Sylvain Audia, Marc Ruivard, Bouchra Asli, Jean‐Pierre Marolleau, Nadine Méaux‐Ruault, Mathieu Gerfaud‐Valentin, Philippe Audeguy, Mohamed Hamidou, Selim Corm, Xavier Delbrel, Jean Fontan, Delphine Lebon, Christelle Mausservey, Guillaume Moulis, Nicolas Limal, Marc Michel, Bertrand Godeau, Matthieu Mahévas, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Edouard Herriot-Lyon, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne (Med Int - BESANCON), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Medipole De Savoie, Service de Médecine Interne [Pau], Centre hospitalier de Pau, Service d'hématologie, and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: ITP, TPO-RA, Hematology, immunosuppressive drug, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, combination therapy
Abstract: International audience; Combining drugs could be an effective option for treating multirefractory ITP, that is, patients not responding to rituximab, thrombopoietin receptor agonists (TPO-RA) and splenectomy. We conducted a retrospective, multicenter, observational study including multirefractory ITP patients who received a combination of a TPO-RA and an immunosuppressive drug. We included 39 patients (67% women, median age 59 years [range 21-96]), with a median ITP duration of 57 months [3-393] and a median platelet count at initiation of 10 × 109 /L [1-35]. The combination regimen was given for a median duration of 12 months [1-103] and included eltrombopag (51%) or romiplostim (49%), associated with mycophenolate mofetil (54%), azathioprine (36%), cyclophosphamide (5%), cyclosporin (3%) or everolimus (3%). Overall, 30 patients (77%) achieved at least a response (platelet count ≥30 × 109 /L and at least doubling baseline during at least 3 months), including 24 complete responses (platelet count >100 × 109 /L during at least 3 months) with a median time to response of 30 days [7-270] and a median duration of response of 15 months [4-63]. Severe adverse event related to ITP treatment was observed in 31%. In conclusion, this study confirms that some patients with multirefractory ITP can achieve long lasting response with this combination.
Published: 2023

10. Supplementary Tables from Carfilzomib Weekly plus Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Multiple Myeloma (IFM 2012-03): A Phase I Trial

Author: Thierry Facon, Cyrille Hulin, Hervé Avet-Loiseau, Philippe Moreau, Michel Attal, Eric G. Voog, Véronique Dorvaux, Jean-Claude Eisenmann, Damien Roos-Weil, Olivier Fitoussi, Jamile Frayfer, Catherine Humbrecht-Kraut, Olivier Decaux, Sophie Rigaudeau, Frédérique Kuhnowski, Sophie Cereja, Laurent Voillat, Fritz Offner, Anna Schmitt, Philippe Rodon, Jean Fontan, Marie-Lorraine Chrétien, Gérard Lepeu, Karim Belhadj-Merzoug, Marie-Odile Pétillon, Arnaud Jaccard, Murielle Roussel, Pascal Lenain, Pascal Bourquard, Jean-Valère Malfuson, Nathalie Meuleman, Carla Araujo, Mourad Tiab, Brigitte Kolb, Lionel Karlin, François Machuron, Alain Duhamel, Stéphanie Guidez, Valentine Richez, Guillemette Fouquet, and Xavier Leleu
Abstract: Supplementary tables 1 to 5
Published: 2023

11. Data from Carfilzomib Weekly plus Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Multiple Myeloma (IFM 2012-03): A Phase I Trial

Author: Thierry Facon, Cyrille Hulin, Hervé Avet-Loiseau, Philippe Moreau, Michel Attal, Eric G. Voog, Véronique Dorvaux, Jean-Claude Eisenmann, Damien Roos-Weil, Olivier Fitoussi, Jamile Frayfer, Catherine Humbrecht-Kraut, Olivier Decaux, Sophie Rigaudeau, Frédérique Kuhnowski, Sophie Cereja, Laurent Voillat, Fritz Offner, Anna Schmitt, Philippe Rodon, Jean Fontan, Marie-Lorraine Chrétien, Gérard Lepeu, Karim Belhadj-Merzoug, Marie-Odile Pétillon, Arnaud Jaccard, Murielle Roussel, Pascal Lenain, Pascal Bourquard, Jean-Valère Malfuson, Nathalie Meuleman, Carla Araujo, Mourad Tiab, Brigitte Kolb, Lionel Karlin, François Machuron, Alain Duhamel, Stéphanie Guidez, Valentine Richez, Guillemette Fouquet, and Xavier Leleu
Abstract: Purpose:Carfilzomib is a novel generation proteasome inhibitor. The Carmysap trial demonstrated that twice-weekly KMP (carfilzomib, melphalan, prednisone) might challenge the MPV (melphalan, prednisone, bortezomib) standard. We sought to study KMP weekly, allowing to increase carfilzomib's dose with maintained efficacy and improved safety profile.Patients and Methods:IFM2012-03, a phase I multicenter study of KMP weekly in elderly patients with newly diagnosed multiple myeloma (eNDMM), aimed to determine the MTD of carfilzomib. Carfilzomib was given intravenously at 36, 45, 56, and 70 mg/m2/day on days 1, 8, 15, and 22 with melphalan and prednisone, for nine 35-day induction cycles, followed by carfilzomib maintenance for 1 year. Three dose-limiting toxicities (DLT) determined MTD at the lower dose.Results:Thirty eNDMMs were treated, 6 per cohort at 36, 45, and 56 mg/m2 and 12 at 70 mg/m². There was one DLT at 36 mg/m2 (lymphopenia), one at 45 mg/m2 (lysis syndrome), two at 56 mg/m2 (cardiac insufficiency and febrile neutropenia), and two at 70 mg/m2 (vomiting and elevated liver enzymes). The safety profile was acceptable; however, specific attention must be paid to the risk of cardiovascular events, especially for elderly patients. The overall response rate was 93.3%, with 46.6% complete response.Conclusions:The MTD dose of carfilzomib was 70 mg/m2 in this KMP weekly study in eNDMM. Response rates, and especially CR rate, were remarkable in this population, and would benefit from being assessed in a larger-scale study. The IFM2012-03 study demonstrated that the MTD of carfilzomib weekly is 70 mg/m2 in eNDMM, and 56 mg/m2 for patients older than 75 years. Carfilzomib used weekly in combination has a good efficacy and safety profile in eNDMM.
Published: 2023

12. Supplementary Figures from Carfilzomib Weekly plus Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Multiple Myeloma (IFM 2012-03): A Phase I Trial

Author: Thierry Facon, Cyrille Hulin, Hervé Avet-Loiseau, Philippe Moreau, Michel Attal, Eric G. Voog, Véronique Dorvaux, Jean-Claude Eisenmann, Damien Roos-Weil, Olivier Fitoussi, Jamile Frayfer, Catherine Humbrecht-Kraut, Olivier Decaux, Sophie Rigaudeau, Frédérique Kuhnowski, Sophie Cereja, Laurent Voillat, Fritz Offner, Anna Schmitt, Philippe Rodon, Jean Fontan, Marie-Lorraine Chrétien, Gérard Lepeu, Karim Belhadj-Merzoug, Marie-Odile Pétillon, Arnaud Jaccard, Murielle Roussel, Pascal Lenain, Pascal Bourquard, Jean-Valère Malfuson, Nathalie Meuleman, Carla Araujo, Mourad Tiab, Brigitte Kolb, Lionel Karlin, François Machuron, Alain Duhamel, Stéphanie Guidez, Valentine Richez, Guillemette Fouquet, and Xavier Leleu
Abstract: Supplementary Figure 1. Complementary survival curves for the whole cohort (n=30). (A) Event Free Survival (EFR); (B) Time to new treatment (TTNT); (C) Duration of response (DOR). Supplementary Figure 2. Progression Free Survival and Overall Survival according to cytogenetic risk (n=30). (A) PFS according to cytogenetic risk; (B) OS according to cytogenetic risk.
Published: 2023

13. Bortezomib and high-dose melphalan conditioning regimen in frontline multiple myeloma: an IFM randomized phase 3 study

Author: Murielle Roussel, Valérie Lauwers-Cances, Margaret Macro, Xavier Leleu, Bruno Royer, Cyrille Hulin, Lionel Karlin, Aurore Perrot, Cyrille Touzeau, Marie-Lorraine Chrétien, Sophie Rigaudeau, Mamoun Dib, Emmanuelle Nicolas-Virelizier, Martine Escoffre-Barbe, Karim Belhadj, Clara Mariette, Anne-Marie Stoppa, Carla Araujo, Chantal Doyen, Jean Fontan, Brigitte Kolb, Laurent Garderet, Sabine Brechignac, Jean-Valère Malfuson, Arnaud Jaccard, Pascal Lenain, Cécile Borel, Benjamin Hebraud, Omar Benbrahim, Véronique Dorvaux, Salomon Manier, Karine Augeul-Meunier, Marie-Christiane Vekemans, Edouard Randriamalala, Driss Chaoui, Jo Caers, Carine Chaleteix, Lofti Benboubker, Laure Vincent, Sylvie Glaisner, Patricia Zunic, Borhane Slama, Jean-Richard Eveillard, Catherine Humbrecht-Kraut, Véronique Morel, Philippe Mineur, Jean-Claude Eisenmann, Hélène Demarquette, Valentine Richez, Marguerite Vignon, Denis Caillot, Thierry Facon, Philippe Moreau, Anne-Laurène Colin, Pascale Olivier, Soraya Wuilleme, Hervé Avet-Loiseau, Jill Corre, Michel Attal, UCL - (MGD) Service d'hématologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne
Subjects: Bortezomib, Antineoplastic Combined Chemotherapy Protocols, Immunology, Humans, Cell Biology, Hematology, Multiple Myeloma, Melphalan, Transplantation, Autologous, Biochemistry
Abstract: High-dose melphalan (HDM) and transplantation are recommended for eligible patients with multiple myeloma. No other conditioning regimen has proven to be more effective and/or safer. We previously reported in a phase 2 study that bortezomib can safely and effectively be combined with HDM (Bor-HDM), with a 32% complete response (CR) rate after transplantation. These data supported a randomized phase 3 trial. Randomization was stratified according to risk and response to induction: 300 patients were enrolled, and 154 were allocated to the experimental arm (ie, arm A) with bortezomib (1 mg/m2 intravenously [IV]) on days −6, –3, +1, and +4 and melphalan (200 mg/m2 IV) on day –2. The control arm (ie, arm B) consisted of HDM alone (200 mg/m2 IV). There were no differences in stringent CR + CR rates at day 60 posttransplant (primary end point): 22.1% in arm A vs 20.5% in arm B (P = .844). There were also no differences in undetectable minimum residual disease rates: 41.3% vs 39.4% (P = .864). Median progression-free survival was 34.0 months for arm A vs 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P = .244). The estimated 3-year overall survival was 89.5% in both arms (hazard ratio, 1.28; 95% CI, 0.62-2.64; P = .374). Sixty-nine serious adverse events occurred in 18.7% of Bor-HDM–treated patients (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at www.clinicaltrials.gov as #NCT02197221.
Published: 2022

14. Clinical characteristics and outcome of 318 families with familial monoclonal gammopathy: A multicenter Intergroupe Francophone du Myélome study

Author: Charles Dumontet, Delphine Demangel, Perrine Galia, Lionel Karlin, Laurent Roche, Mathieu Fauvernier, Camille Golfier, Marie‐Charlotte Laude, Xavier Leleu, Philippe Rodon, Murielle Roussel, Isabelle Azaïs, Chantal Doyen, Borhane Slama, Salomon Manier, Olivier Decaux, Maroulio Pertesi, Marie Beaumont, Denis Caillot, Eileen M. Boyle, Manuel Cliquennois, Pascale Cony‐Makhoul, Anne‐Violaine Doncker, Véronique Dorvaux, Marie Odile Petillon, Jean Fontan, Bénédicte Hivert, Isabelle Leduc, Cécile Leyronnas, Margaret Macro, Michel Maigre, Clara Mariette, Philippe Mineur, Sophie Rigaudeau, Bruno Royer, Laure Vincent, James Mckay, Emeline Perrial, Laurent Garderet, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Fédération Française pour la Recherche contre le Myélome et les Gammapathies (FFRMG) Institut National Du Cancer, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie
Subjects: Chromosome Aberrations, MESH: Humans, Paraproteinemias, MESH: Multiple Myeloma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Prognosis, Monoclonal Gammopathy of Undetermined Significance, MESH: Prognosis, MESH: Paraproteinemias, MESH: Child, MESH: Monoclonal Gammopathy of Undetermined Significance, Humans, MESH: Chromosome Aberrations, Child, Multiple Myeloma
Abstract: International audience; Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full-blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow-up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.
Published: 2023

15. Multicenter Open Label Phase 2 Study of Isatuximab Plus Pomalidomide and Dexamethasone with Carfilzomib in Relapsed or Refractory Multiple Myeloma. Iskpd - IFM2018-03

Author: Arthur Bobin, Jerome Lambert, Stéphanie Ragot, Aurore Perrot, Salomon Manier, Lionel Karlin, Denis Caillot, Cyrille Hulin, Lotfi Benboubker, Carla Araujo, Jean Fontan, Thorsten Braun, Clara Mariette, Elodie Scherman, Olivier Decaux, jean Sebastien Blade, Faida Keddar, Christophe Roul, Mamoun Dib, Jill Corre, Frederique Orsini, Laure Vincent, Mohamad Mohty, Cyrille Touzeau, Philippe Moreau, Herve Avet Loiseau, Xavier Leleu, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)
Subjects: Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Hematology, Biochemistry
Published: 2022

16. Vaccination coverage in hematological patients undergoing chemotherapy: Should we move towards personalized vaccination?

Author: Ana Berceanu, Alix Pierron, Catherine Chirouze, Jean Fontan, F. Bozon, Anne-Sophie Brunel, Erick Deconinck, and Annie Brion
Subjects: Pediatrics, medicine.medical_specialty, Vaccination Coverage, Vaccination schedule, medicine.medical_treatment, Population, Logistic regression, Pneumococcal Infections, Pneumococcal Vaccines, Humans, Medicine, education, Aged, Chemotherapy, education.field_of_study, General Veterinary, General Immunology and Microbiology, business.industry, Public health, Vaccination, Public Health, Environmental and Occupational Health, Infectious Diseases, Influenza Vaccines, Vaccination coverage, Molecular Medicine, Day hospital, business
Abstract: Introduction Immunocompromised patients are at high-risk for severe influenza and invasive pneumococcal diseases (IPD). Despite the French Public Health Council (FPHC) and the 7th European Conference on Infections in Leukaemia (ECIL7) recommendations, vaccination coverage remains insufficient. This study aimed to estimate the coverage and determinants of influenza, pneumococcal and diphtheria-tetanus-poliomyelitis (dTP) vaccinations in hematological patients underlying chemotherapy. Methods A survey was distributed to all patients of the hematology day hospital assessing vaccine uptakes and general opinion about vaccination. Vaccine uptakes were collected from medical and vaccination records; knowledge of and attitudes towards vaccinations in immunocompromised patients were evaluated for each general practitioner (GP) by phone call. Adequacy between vaccine uptakes and indication or not to vaccinate according to ECIL7 guidelines was assessed. Factors associated with vaccine uptakes were assessed by multivariate logistic regression. Results Among 145 patients, 66 % were aged 65 years or older, 40 % were followed for lymphoma and 38 % for multiple myeloma, 39 % were treated with anti-CD20 antibodies. Vaccination coverage was suboptimal for influenza (45-56 %), dTP (44 %) and IPD (16-19 %) regardless of the guidelines followed, with a wide variation in rates by information source (19-76 %). Adequacy rate with ECIL7 recommendations were 63 % and 87 % for influenza and IPD respectively. Information of patients on specific vaccinations was positively associated with flu and IPD vaccinations, as well as favorable attitude toward vaccination and age ≥ 65 years for flu vaccination, and recommendation by hematologist for pneumococcal vaccination. Conclusion Despite vaccination opportunities, the complexity of these specific recommendations and the lack of communication between the health actors could explain the suboptimal vaccination coverage in this high-risk population. A proactive attitude of all actors in the city and hospital, including better patient information and a personalized and evolving vaccination schedule to help GPs to coordinate vaccination would allow to improve vaccine coverage.
Published: 2021

17. Improved survival in multiple myeloma during the 2005–2009 and 2010–2014 periods

Author: Claudine Sohn, Denis Caillot, Intergroupe Francophone du Myelome, Valentine Richez, Lauriane Clement-Filliatre, Hervé Avet-Loiseau, Lionel Karlin, Karim Belhadj, Philippe Collet, Mourad Tiab, Philippe Moreau, Mamoun Dib, Sabine Brechignac, Jean Fontan, Borane Slama, Cyrille Hulin, François Lifermann, Margaret Macro, Thierry Facon, Mohamad Mohty, Philippe Rey, Hélène Demarquette, Aurore Perrot, Jill Corre, Clara Mariette, Anne-Marie Stoppa, Xavier Leleu, Frédérique Orsini-Piocelle, Laurent Voillat, and Jean-Pierre Marolleau
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, MEDLINE, Improved survival, Signs and symptoms, Hematology, medicine.disease, Text mining, Internal medicine, medicine, business, Multiple myeloma
Published: 2021

18. Carfilzomib maintenance in newly diagnosed non-transplant eligible multiple myeloma

Author: Sophie Cereja, Damien Roos-Weil, Laurent Voillat, Marie-Odile Petillon, Véronique Dorvaux, Marie-Lorraine Chretien, Nathalie Meuleman, Hervé Avet-Loiseau, Arthur Bobin, Olivier Fitoussi, Carla Araujo, Murielle Roussel, Eric Voog, Frédérique Kuhnowski, Intergroupe Francophone du Myelome Multiple, Jean Claude Eisenmann, Mourad Tiab, Catherine Humbrecht-Kraut, Thierry Facon, Jean-Valère Malfuson, Brigitte Kolb, Karim Belhadj-Merzoug, Philippe Rodon, Pascal Bourquard, Lionel Karlin, Olivier Decaux, Maeva Kyheng, Valentine Richez, Sophie Rigaudeau, Jamile Frayfer, Xavier Leleu, Philippe Moreau, Arnaud Jaccard, Alain Duhamel, Aurore Perrot, Pascal Lenain, Cyrille Hulin, Cécile Gruchet-Merouze, Jean Fontan, Anna Schmitt, Stéphanie Guidez, Fritz Offner, INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Limoges, Hôpital Henri Mondor, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Bergonié [Bordeaux], UNICANCER, Institut Curie [Paris], CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], Amgen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Université de Poitiers, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], MEDLINE, Antineoplastic Agents, Newly diagnosed, Maintenance Chemotherapy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, business.industry, Hematology, medicine.disease, Carfilzomib, Progression-Free Survival, 3. Good health, chemistry, 030220 oncology & carcinogenesis, Multiple Myeloma, business, Oligopeptides
Abstract: International audience
Published: 2022

19. Primary plasma cell leukemias displaying t(11;14) have specific genomic, transcriptional, and clinical features

Author: Titouan Cazaubiel, Xavier Leleu, Aurore Perrot, Salomon Manier, Laure Buisson, Sabrina Maheo, Laura Do Souto Ferreira, Romain Lannes, Luka Pavageau, Cyrille Hulin, Jean-Pierre Marolleau, Laurent Voillat, Karim Belhadj, Marion Divoux, Borhane Slama, Sabine Brechignac, Margaret Macro, Anne-Marie Stoppa, Laurence Sanhes, Frédérique Orsini-Piocelle, Jean Fontan, Marie-Lorraine Chretien, Hélène Demarquette, Mohamad Mohty, Anais Schavgoulidze, Herve Avet-Loiseau, Jill Corre, Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Lille, Service des maladies du sang, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Chalon-sur-Saône William Morey, Hôpital Henri Mondor, Université de Lorraine (UL), Avignon Université (AU), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Saint Jean de Perpignan, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Claude Huriez [Lille], CHU Lille, CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Purpan (CHU Purpan), and CHU Toulouse [Toulouse]
Subjects: Chromosome Aberrations, [SDV]Life Sciences [q-bio], Immunology, Humans, Cell Biology, Hematology, Genomics, Multiple Myeloma, Prognosis, Transcriptome, Biochemistry, Leukemia, Plasma Cell
Abstract: Primary plasma cell leukemia (pPCL) is an aggressive form of multiple myeloma (MM) that has not benefited from recent therapeutic advances in the field. Because it is very rare and heterogeneous, it remains poorly understood at the molecular level. To address this issue, we performed DNA and RNA sequencing of sorted plasma cells from a large cohort of 90 newly diagnosed pPCL and compared with MM. We observed that pPCL presents a specific genomic landscape with a high prevalence of t(11;14) (about half) and high-risk genomic features such as del(17p), gain 1q, and del(1p32). In addition, pPCL displays a specific transcriptome when compared with MM. We then wanted to characterize specifically pPCL with t(11;14). We observed that this subentity displayed significantly fewer adverse cytogenetic abnormalities. This translated into better overall survival when compared with pPCL without t(11;14) (39.2 months vs 17.9 months, P = .002). Finally, pPCL with t(11;14) displayed a specific transcriptome, including differential expression of BCL2 family members. This study is the largest series of patients with pPCL reported so far.
Published: 2022

20. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial

Author: Matthijs Westerman, Bertrand Arnulf, Frédérique Kuhnowski, Tahamtan Ahmadi, Annemiek Broijl, Lotfi Benboubker, Marie-Christiane Vekemans, Sonja Zweegman, Xavier Leleu, Maria Krevvata, Cyrille Touzeau, Veronique Vanquickelberghe, Hélène Caillon, Denis Caillot, Ke Zhang, Soraya Wuilleme, Pieter Sonneveld, Michel Delforge, Mark-David Levin, Jean-Richard Eveillard, Jill Corre, Aurore Perrot, Philippe Moreau, Mohamad Mohty, Nathalie Meuleman, Anne-Marie Stoppa, Jessica Vermeulen, Kon-Siong Jie, Saskia K. Klein, Tobias Kampfenkel, Fritz Offner, Thierry Facon, Hervé Avet-Loiseau, Chantal Doyen, Frédérique Orsini-Piocelle, Cécile Sonntag, Murielle Roussel, Carla de Boer, Jean-Pierre Marolleau, Reda Garidi, Thomas Dejoie, Mourad Tiab, Cyrille Hulin, Lionel Karlin, Margaret Macro, Jean Fontan, Sanjay Vara, Jérôme J. Lambert, Niels W.C.J. van de Donk, Marie C. Béné, Martine Escoffre-Barbe, Karim Belhadj, Hematology, CCA - Cancer Treatment and quality of life, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service d'hématologie, and UCL - (SLuc) Service d'hématologie
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, Population, Transplantation, Autologous, Dexamethasone, Drug Administration Schedule, Maintenance Chemotherapy, Bortezomib, Young Adult, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Medicine, Data monitoring committee, Humans, education, Multiple myeloma, Aged, education.field_of_study, business.industry, Hazard ratio, Daratumumab, Antibodies, Monoclonal, Middle Aged, medicine.disease, Interim analysis, Progression-Free Survival, Thalidomide, Europe, Oncology, Female, business, Multiple Myeloma, medicine.drug, Stem Cell Transplantation
Abstract: Background: CASSIOPEIA part 1 showed superior depth of response and significantly improved progression-free survival with daratumumab, bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) as induction and consolidation in patients with autologous stem-cell transplant (ASCT)-eligible newly diagnosed multiple myeloma. In part 2, we compared daratumumab maintenance versus observation only. Methods: CASSIOPEIA is a two-part, open-label, randomised, phase 3 trial of patients aged 18–65 years with newly diagnosed multiple myeloma and Eastern Cooperative Oncology Group performance status 0–2, done in 111 European academic and community practice centres. In part 1, patients were randomly assigned (1:1) to induction and consolidation with D-VTd or VTd. Patients still on study who had a partial response or better were randomly assigned (1:1) by an interactive web-response system to daratumumab 16 mg/kg intravenously every 8 weeks (a reduced frequency compared with standard daratumumab long-term dosing) or observation only for up to 2 years. Stratification factors were induction treatment and depth of response in part 1. The part 2 primary endpoint was progression-free survival from second randomisation. This preplanned interim analysis of progression-free survival was done after 281 events and shall be considered the primary analysis of progression-free survival. Sponsor personnel and designees who were involved in the analysis were masked to treatment group until the independent data monitoring committee recommended that the preplanned interim analysis be considered the main analysis of progression-free survival in part 2. Otherwise, treatment assignments were unmasked. The interaction between induction and consolidation and maintenance was tested at a two-sided significance level of 0·05 by a stratified Cox regression model that included the interaction term between maintenance treatment and induction and consolidation treatment. Efficacy analyses were done in the maintenance-specific intention-to-treat population, which comprised all patients who underwent second randomisation. Safety was analysed in all patients in the daratumumab group who received at least one dose and all patients randomly assigned to observation only. This trial is registered with ClinicalTrials.gov, NCT02541383. Long-term follow-up is ongoing and the trial is closed to new participants. Findings: Between May 30, 2016, and June 18, 2018, 886 patients (458 [84%] of 543 in the D-VTd group and 428 [79%] of 542 in the VTd group) were randomly assigned to daratumumab maintenance (n=442) or observation only (n=444). At a median follow-up of 35·4 months (IQR 30·2–39·9) from second randomisation, median progression-free survival was not reached (95% CI not evaluable [NE]–NE) with daratumumab versus 46·7 months (40·0–NE) with observation only (hazard ratio 0·53, 95% CI 0·42–0·68, p
Published: 2021

21. Immune Thrombocytopenia Revealing Enriched IgG-4 Peri-Renal Rosai-Dorfman Disease Successfully Treated with Rituximab: A Case Report and Literature Review

Author: Sylvain Audia, Sébastien Humbert, Jean Fontan, Fleur Cohen-Aubart, Jean-François Emile, Philippe Maksud, Jerome Razanamahery, Julien Haroche, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de médecine nucléaire [CHU Pitié-Salpétrière], and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: Medicine (General), [SDV]Life Sciences [q-bio], Case Report, 03 medical and health sciences, 0302 clinical medicine, R5-920, rituximab, immune system diseases, hemic and lymphatic diseases, Biopsy, medicine, Platelet, Rosai–Dorfman disease, Histiocyte, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, Pathophysiology, 3. Good health, Histiocytosis, Rosai Dorfman disease, immune thrombocytopenia, 030220 oncology & carcinogenesis, Erdheim Chester disease, Immunology, Erdheim–Chester disease, Medicine, Rituximab, business, histiocytosis, 030215 immunology, medicine.drug
Abstract: Immune thrombocytopenia (ITP) is a rare autoimmune-mediated condition characterized by isolated thrombocytopenia (MAP2K1mutation, although peri-renal infiltration is highly suggestive of Erdheim-Chester disease. This overlapping association was described in men with mutation inMAP2K1gene. Macrophages are implicated in the pathophysiology of ITP in multiple ways, notably by the phagocytosis of opsonized platelets and their function of antigen-presenting cells able to stimulate autoreactive T cells. Histiocytic cells derivate from monocyte-macrophage lineage. Activation of macrophages in active histiocytosis is responsible for consequential platelet destruction in ITP associated histiocytosis. Finally, this case highlights a rare presentation of ITP revealing histiocytosis, both being efficiently treated with rituximab.
Published: 2021

22. Oral therapy adherence and satisfaction in patients with multiple myeloma

Author: Anne Rumpler, Jean Fontan, Coline Pain, Cyril Faure, Pierre Loriod, Marie Kroemer, Pauline Marguet, Marine Solano, Anne-Cécile Maes, Samuel Limat, Eric Deconinck, Anne-Laure Clairet, and Etienne Daguindau
Subjects: Male, medicine.medical_specialty, Pharmacist, Administration, Oral, Personal Satisfaction, Hospitals, General, Medication Adherence, Hospitals, University, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Internal medicine, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Prospective Studies, Risk factor, Multiple myeloma, Aged, Response rate (survey), Univariate analysis, business.industry, Hematology, General Medicine, Middle Aged, medicine.disease, Clinical pharmacy, Cross-Sectional Studies, Caregivers, Socioeconomic Factors, Patient Satisfaction, 030220 oncology & carcinogenesis, Observational study, Female, France, business, Multiple Myeloma, 030215 immunology
Abstract: The transition to oral therapies in patients with multiple myeloma (MM) offers potential benefits to patients; however, they must self-manage their medication and adherence plays an important role in patient care. It has been shown that patient satisfaction with their medication has a strong positive correlation with adherence in chronic diseases. The aim of this study was to estimate adherence rate of oral antimyeloma therapies and to identify risk factors for medication non-adherence. This observational, prospective, and multicentre survey based on a self-report questionnaire enrolled MM patients with at least 3 months of oral therapy. The 6-item Girerd scale and the medication possession ratio (MPR) were used for measuring medication adherence and the SATMED-Q® questionnaire was used for measuring satisfaction. An analysis of risk factors for non-adherence to oral therapy was performed using univariate analysis. A total of 101 patients participated in the survey, yielding a response rate of 87%. The prevalence of adherence to oral antimyeloma therapy was estimated at 51.5% using the Girerd questionnaire. According to the MPR, adherence was evaluated at 96% (i.e. MPR ≥ 0.80). Both methods combined, adherence was estimated at 50.5%. One risk factor for medication non-adherence was identified: Eastern Cooperative Oncology Group Performance Status > 2 (p = 0.007). One predictive factor for high medication adherence was identified: high satisfaction with treatment (p = 0.01). Identifying patients at higher risk for non-adherence allows clinical pharmacists to personalise therapeutic information and education and to improve the quality of healthcare overall.
Published: 2021

23. Epidemiological landscape of young patients with multiple myeloma diagnosed before 40 years of age: the French experience

Author: Pierre Morel, Anne-Marie Stoppa, Hervé Avet-Loiseau, Benoit Branco, Bruno Royer, Murielle Roussel, Valentine Richez, Chantal Doyen, Clara Mariette, Denis Caillot, Sarah Ivanoff, Laurent Garderet, Cyrille Hulin, Bertrand Arnulf, Jean Galtier, Jean Fontan, Naelle Lombion, Alexis Caulier, Aurore Perrot, Pascal Lenain, Xavier Leleu, Anne-Victoire Michaud-Robert, Cyrille Touzeau, Jean-Pierre Marolleau, Stephanie Harel, Salomon Manier, CHU Amiens-Picardie, CHU Limoges, CHU Bordeaux [Bordeaux], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service hématologie Nice, Centre Hospitalier Universitaire de Nice (CHU Nice), Département de Médecine Nucléaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [Nantes], Site de Recherche Intégrée sur le Cancer [Nantes] (SIRIC), Imaging and Longitudinal Investigations to Ameliorate Decision-making [Nantes] (ILIAD), Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), UCL - (MGD) Service d'hématologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne
Subjects: Adult, Male, medicine.medical_specialty, Multivariate analysis, Anemia, BLOOD COMMENTARY, [SDV]Life Sciences [q-bio], Immunology, Transplantation, Autologous, Biochemistry, Young Adult, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Epidemiology, medicine, Humans, Multiple myeloma, business.industry, Age Factors, Hematopoietic Stem Cell Transplantation, Cytogenetics, Cell Biology, Hematology, medicine.disease, Progression-Free Survival, Transplantation, Treatment Outcome, Female, Disease characteristics, France, Stem cell, Multiple Myeloma, business, Follow-Up Studies
Abstract: Multiple myeloma (MM) is rare in young patients, especially before age 40 years at diagnosis, representing
Published: 2021

24. del(17p) without TP53 mutation confers a poor prognosis in intensively treated newly diagnosed patients with multiple myeloma

Author: Jill Corre, Denis Caillot, Jean-Pierre Marolleau, Naïs Prade, Philippe Moreau, Mamoun Dib, Karim Belhadj, Jean Fontan, Arnaud Jaccard, Sabine Brechignac, Stephane Minvielle, Laurence Sanhes, Margaret Macro, Laure Buisson, Lionel Karlin, Xavier Leleu, Hervé Avet-Loiseau, Thierry Facon, Laurent Voillat, Romain Lannes, Aurore Perrot, Mohamad Mohty, Frédérique Orsini-Piocelle, Stephanie Dufrechou, Lauriane Clement-Filliatre, Cyrille Hulin, and Laura Do Souto
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Immunology, Population, Newly diagnosed, Tp53 mutation, Biochemistry, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, Young adult, education, Multiple myeloma, Aged, Extremely Poor, education.field_of_study, business.industry, Cell Biology, Hematology, Middle Aged, medicine.disease, Prognosis, 3. Good health, Chromosome 17 (human), 030220 oncology & carcinogenesis, Cohort, Mutation, Female, Chromosome Deletion, Tumor Suppressor Protein p53, business, Multiple Myeloma, 030215 immunology, Chromosomes, Human, Pair 17
Abstract: Despite tremendous improvements in the outcome of patients with multiple myeloma in the past decade, high-risk patients have not benefited from the approval of novel drugs. The most important prognostic factor is the loss of parts of the short arm of chromosome 17, known as deletion 17p (del(17p)). A recent publication (on a small number of patients) suggested that these patients are at very high-risk only if del(17p) is associated with TP53 mutations, the so-called “double-hit” population. To validate this finding, we designed a much larger study on 121 patients presenting del(17p) in > 55% of their plasma cells, and homogeneously treated by an intensive approach. For these 121 patients, we performed deep next generation sequencing targeted on TP53. The outcome was then compared with a large control population (2505 patients lacking del(17p)). Our results confirmed that the “double hit” situation is the worst (median survival = 36 months), but that del(17p) alone also confers a poor outcome compared with the control cohort (median survival = 52.8 months vs 152.2 months, respectively). In conclusion, our study clearly confirms the extremely poor outcome of patients displaying “double hit," but also that del(17p) alone is still a very high-risk feature, confirming its value as a prognostic indicator for poor outcome.
Published: 2020

25. Improved survival in multiple myeloma during the 2005-2009 and 2010-2014 periods

Author: Jill, Corre, Aurore, Perrot, Cyrille, Hulin, Denis, Caillot, Anne-Marie, Stoppa, Thierry, Facon, Xavier, Leleu, Mamoun, Dib, Lionel, Karlin, Philippe, Moreau, Mohamad, Mohty, Clara, Mariette, Jean, Fontan, Jean-Pierre, Marolleau, Hélène, Demarquette, Borane, Slama, Laurent, Voillat, Margaret, Macro, Frédérique, Orsini-Piocelle, Sabine, Brechignac, Philippe, Rey, Philippe, Collet, Mourad, Tiab, Karim, Belhadj, François, Lifermann, Lauriane, Clement-Filliatre, Claudine, Sohn, Valentine, Richez, and Hervé, Avet-Loiseau
Subjects: Adult, Aged, 80 and over, Hematopoietic Stem Cell Transplantation, Middle Aged, Transplantation, Autologous, Survival Rate, Young Adult, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Humans, France, Multiple Myeloma, Aged, Retrospective Studies
Published: 2020

26. RD Vs. VRD: What Is the First-Line, Real-Life Management of Multiple Myeloma Patients Ineligible for Stem Cell Auto Transplantation in the Emmy Cohort?

Author: Ronan Garlantezec, Carla Araujo, Nathalie Texier, Xavier Leleu, Olivier Decaux, Bruno Royer, Valentine Richez, Anne Vekhoff, Karim Belhadj, Cyrille Hulin, Arnaud Jaccard, Agathe Farge, Laurent Frenzel, Aurore Perrot, Frederique Orsini, Jean Fontan, Philippe Moreau, Laurence Sanhes, Catherine Boccaccio, Raphaël Germain, Denis Caillot, and Samantha Schulmann
Subjects: Oncology, medicine.medical_specialty, business.industry, First line, Immunology, Cell Biology, Hematology, medicine.disease, Biochemistry, Transplantation, Internal medicine, Cohort, medicine, Stem cell, business, Life management, Multiple myeloma
Abstract: Background In recent years, large clinical trials have shown the superiority of L1 RD (lenalidomide-dexamethasone) over MPT, and then L1 VRD (lenalidomide, bortezomib and dexamethasone) over RD in Multiple Myeloma (MM) patients ineligible for autologous stem cell transplantation (ASCT). The EMMY study, a large-scale epidemiological study to assess the epidemiology and real-life management of multiple myeloma (MM), describes the real-life use and efficacy of RD and VRD regimens in first-line patients not eligible for ASCT (non ASCT-L1). Methods EMMY is a descriptive, multicenter, national, non-interventional study conducted in 72 IFM (Intergroupe Francophone du Myélome, sponsor) centers in France. Any patient initiating treatment for MM over a 3-month observation period, from October to December, is included, since 2017. It is a dynamic cohort with the inclusion of 1000 additional patients each year (2765 patients included at the end of 2019). Data are updated annually from hospital records up to 2020. The sample of patients receiving RD or VRD therapy in the non ASCT-L1 patient group, over the 2017-2019 period, was extracted to describe patient characteristics. The time to next treatment (TNT), and overall survival (OS) were estimated. The strategies were compared in the subgroup of patients aged of [65-75[ year-old (Wilcoxon test). Results Among the 773 EMMY patients initiating a non ASCT-L1 treatment during the period 2017-2019, 162 (21%) received RD and 158 (20%) VRD. The median follow-up was 22 months (RD) and 11 months (VRD). Other patients received MPV (26%, n=204), VCD (13%, n=101), VD (8%, n=61), VTD (5%, n=37) or other combinations (7%, n=50). Median age was 79.6 [73.7-83.1] and 69.3 [64.7-73.2] years at initiation of RD and VRD. When available, other characteristics were similar between the 2 groups: ECOG ≥ 2 for 31% (RD) (n= 23/ 74) and 26% (VRD) (n=17/65), high cytogenetic risk for 13% (RD) (n=9/67) and 12% (VRD) (n=9/77), ISS at 1/2/3 for 32, 28, and 40% (RD) (n= 83) and 33, 23, and 44% (VRD) (n= 87) of patients. ASCT was initially planned for 23 of 82 patients initiating VRD in late 2019. The mTNT was 29.1 months 95%IC [20.1-37.7] in RD patients and 34.1 months 95%IC [24.1 - NA] in VRD patients. For patients who received other combinaison in non ASCT-L1, mTTNT varied from 5.2 months 95%IC [3.6 - 12.6] (VRD) and 5.3 months 95%IC [3.9 -15.3] (VD) to 13 months 95%IC [9.2 - 24.7] (VCD), 13 months 95%IC [9.2 - 20.3] (other) and 20.3 months 95%IC [17.2 - 24] (MPV) (p The mTNT by age ( OS at 24 months was 86% [78; 91] and 85% [75; 91] for the RD and VRD groups, respectively. Of the 55 RD patients who relapsed and initiated L2, 46 (84%) received bortezomib (MPV 26%, DVD 16%, VD 18%, and VCD 11%). The 39 VRD patients with initiated L2 received IMID (72%) and/or anti CD38 (50%) in various strategies (DPomDex 17%, DRD 14%, DVD 6%). By focusing on the [65-75[ year old patient group (n=135, including 48 RD and 87 VRD patients), the 12 and 24 month TTNT rates were respectively 67% [54;85] and 55% [40;71] in the RD group (n=48) vs 85% [77-92] and 71% [58-84] in the VRD group (n=87) (p.0,01). In this subgroup RD patients were slightly older (72 vs 70 year-old) with ECOG≥2 in 41% vs 18%. Conclusion RD and VRD stragegies improve TTNT in non ASCT L1 patients. RD is predominantly prescribed to patients ≥75 years of age in whom it remains highly effective. For patients ≥75 years of age, prescription of VRD does not appear to provide significant benefit vs. RD. For those Figure 1 Figure 1. Disclosures Decaux: Amgen BMS Celgene Janssen Sanofi Takeda: Honoraria. Perrot: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria. Moreau: Sanofi: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Celgene BMS: Honoraria; Oncopeptides: Honoraria. Leleu: Roche: Honoraria; Pierre Fabre: Honoraria; Oncopeptides: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Merck: Honoraria; Karyopharm Therapeutics: Honoraria; Janssen-Cilag: Honoraria; Gilead Sciences: Honoraria; Celgene: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Bristol-Myers Squibb: Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Other: Non-financial support; Amgen: Honoraria; AbbVie: Honoraria. Sanhes: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Jaccard: Abbvie: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Boccaccio: celgene: Current holder of individual stocks in a privately-held company. Hulin: Celgene/BMS: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; abbvie: Honoraria.
Published: 2021

27. Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma

Author: Karim Belhadj, Mamoun Dib, Jean Fontan, Jean-Michel Pignon, Carla Araujo, Philippe Rodon, Mourad Tiab, Chantal Doyen, Sabine Brechignac, Margaret Macro, Xavier Leleu, Michel Attal, Laurent Voillat, Lionel Karlin, Jill Corre, Olivier Fitoussi, Pascal Godmer, Eileen M Boyle, Marie-Lorraine Chretien, Hervé Avet-Loiseau, Murielle Roussel, Olivier Allangba, Nathalie Meuleman, Hélène Caillon, Olivier Decaux, Frédérique Orsini-Piocelle, Thomas Dejoie, Bertrand Arnulf, Lotfi Benboubker, Odile Luycx, Mohamad Mohty, Laurent Garderet, Denis Caillot, Cyrille Hulin, Aurore Perrot, Pascal Lenain, Thierry Facon, Jean-Gabriel Fuzibet, Laurence Legros, Charlotte Fontan, Philippe Moreau, Brigitte Pegourie, Anne-Marie Stoppa, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Général de La Roche sur Yon, Centre Hospitalier de Bretagne Atlantique, Centre Hospitalier Dunkerque, Département Universitaire Nice, Hôpital de Nice, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital universitaire de Lyon, Hôpital Universitaire de Lyon, Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [APHP], ALWP-EBMT & Département d'hématologie et de thérapie cellulaire [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Service d'Hématologie, CRLCC Henri Becquerel, Hôpital Universitaire de Caen, Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut des Matériaux Jean Rouxel (IMN), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Laboratoire de Biochimie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Universitaire de Bobigny, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Chalon-sur-Saône William Morey, Polyclinique Bordeaux Nord Aquitaine, Hôpital Universitaire de Tours, Centre de Recherche en Cancérologie de Toulouse ( CRCT ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Paoli Calmettes, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Universitaire du Cancer de Toulouse - Oncopole ( IUCT Oncopole - UMR 1037 ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Institut des Materiaux de Nantes [Nantes] ( IMN ), Université de Nantes ( UN ) -Centre National de la Recherche Scientifique ( CNRS ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Claude Huriez [Lille], CHU Lille, Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Polyclinique Bordeaux Nord Aquitaine (PBNA), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM)
Subjects: Adult, medicine.medical_specialty, Pathology, Immunology, Urology, Urine, Immunoglobulin light chain, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Humans, Medicine, Survival analysis, Multiple myeloma, Proportional Hazards Models, [SDV.GEN]Life Sciences [q-bio]/Genetics, Free Immunoglobulin Light Chain, business.industry, Induction Chemotherapy, Cell Biology, Hematology, Middle Aged, Reference Standards, medicine.disease, Survival Analysis, Minimal residual disease, 3. Good health, Consolidation Chemotherapy, 030220 oncology & carcinogenesis, Predictive value of tests, Monoclonal, Immunoglobulin Light Chains, Multiple Myeloma, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, business, 030215 immunology
Abstract: International audience; Guidelines for monitoring multiple myeloma (MM) patients expressing light chains only (light-chain MM [LCMM]) rely on measurements of monoclonal protein in urine. Alternatively, serum free light chain (sFLC) measurements have better sensitivity over urine methods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here, we compared performance of serum and urine measurements in 113 (72κ, 41λ) newly diagnosed LCMM patients enrolled in the Intergroupe Francophone du Myélome (IFM) 2009 trial. All diagnostic samples (100%) had an abnormal κ:λ sFLC ratio, and involved (monoclonal) FLC (iFLC) expressed at levels deemed measurable for monitoring (≥100 mg/L). By contrast, only 64% patients had measurable levels of monoclonal protein (≥200 mg per 24 hours) in urine protein electrophoresis (UPEP). After 1 and 3 treatment cycles, iFLC remained elevated in 71% and 46% of patients, respectively, whereas UPEP reported a positive result in 37% and 18%; all of the patients with positive UPEP at cycle 3 also had elevated iFLC levels. Importantly, elevated iFLC or an abnormal κ:λ sFLC ratio after 3 treatment cycles associated with poorer progression-free survival (P = .006 and P < .0001, respectively), whereas positive UPEP or urine immunofixation electrophoresis (uIFE) did not. In addition, patients with an abnormal κ:λ sFLC ratio had poorer overall survival (P = .022). Finally, early normalization of κ:λ sFLC ratio but not negative uIFE predicted achieving negative minimal residual disease, as determined by flow cytometry, after consolidation therapy (100% positive predictive value). We conclude that improved sensitivity and prognostic value of serum over urine measurements provide a strong basis for recommending the former for monitoring LCMM patients.
Published: 2016

28. Development and Validation of a Cytogenetic Prognostic Index Predicting Survival in Multiple Myeloma

Author: Philippe Moreau, Philippe Rodon, Marie-Lorraine Chretien, Hervé Avet-Loiseau, Olivier Decaux, Cyrille Hulin, Sabine Brechignac, Hélène Demarquette, Xavier Leleu, Michel Attal, Bruno Royer, Laurent Voillat, Philippe Collet, Jill Corre, Aurore Perrot, Margaret Macro, Frédérique Orsini-Piocelle, François Lifermann, Karim Belhadj, Thierry Facon, Arnaud Jaccard, Valérie Lauwers-Cances, Stephane Minvielle, Mohamad Mohty, Elodie Tournay, Valentine Richez, Mamoun Dib, Jean Fontan, Claudine Sohn, Centre hospitalier universitaire de Nantes (CHU Nantes), and Minvielle, Stéphane
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Validation study, Disease free survival, Multivariate analysis, Chromosomes, Human, Pair 21, Trisomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Disease-Free Survival, Translocation, Genetic, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Survival analysis, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, Extramural, business.industry, ORIGINAL REPORTS, Middle Aged, Gene deletion, Prognosis, medicine.disease, Survival Analysis, 3. Good health, Multicenter study, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Multivariate Analysis, Chromosomes, Human, Pair 5, Female, Chromosomes, Human, Pair 3, Multiple Myeloma, business, Gene Deletion
Abstract: PURPOSE The wide heterogeneity in multiple myeloma (MM) outcome is driven mainly by cytogenetic abnormalities. The current definition of high-risk profile is restrictive and oversimplified. To adapt MM treatment to risk, we need to better define a cytogenetic risk classification. To address this issue, we simultaneously examined the prognostic impact of del(17p); t(4;14); del(1p32); 1q21 gain; and trisomies 3, 5, and 21 in a cohort of newly diagnosed patients with MM. METHODS Data were obtained from 1,635 patients enrolled in four trials implemented by the Intergroupe Francophone du Myélome. The oldest collection of data were used for model development and internal validation. For external validation, one of the two independent data sets was used to assess the performance of the model in patients treated with more current regimens. Six cytogenetic abnormalities were identified as clinically relevant, and a prognostic index (PI) that was based on the parameter estimates of the multivariable Cox model was computed for all patients. RESULTS In all data sets, a higher PI was consistently associated with a poor survival outcome. Dependent on the validation cohorts used, hazard ratios for patients in the high-risk category for death were between six and 15 times higher than those of patients in the low-risk category. Among patients with t(4;14) or del(17p), we observed a worse survival in those classified in the high-risk category than in those in the intermediate-risk category. The PI showed good performance for discriminating between patients who died and those who survived (Harrell’s concordance index greater than 70%). CONCLUSION The cytogenetic PI improves the classification of newly diagnosed patients with MM in the high-risk group compared with current classifications. These findings may facilitate the development of risk-adapted treatment strategies.
Published: 2019

29. Carfilzomib Weekly plus Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Multiple Myeloma (IFM 2012-03): A Phase I Trial

Author: Pascal Lenain, Sophie Rigaudeau, Cyrille Hulin, Jean Fontan, Catherine Humbrecht-Kraut, Marie-Lorraine Chretien, Hervé Avet-Loiseau, Frédérique Kuhnowski, Philippe Moreau, Jean Claude Eisenmann, Karim Belhadj-Merzoug, Murielle Roussel, Damien Roos-Weil, Marie-Odile Petillon, Alain Duhamel, Brigitte Kolb, Stéphanie Guidez, Jean Valère Malfuson, Véronique Dorvaux, Michel Attal, Anna Schmitt, Nathalie Meuleman, Valentine Richez, Sophie Cereja, François Machuron, Lionel Karlin, Olivier Decaux, Laurent Voillat, Thierry Facon, Fritz Offner, Mourad Tiab, Olivier Fitoussi, Pascal Bourquard, Guillemette Fouquet, Gérard Lepeu, Arnaud Jaccard, Xavier Leleu, Philippe Rodon, Jamile Frayfer, Carla Araujo, and Eric Voog
Subjects: Male, Melphalan, Oncology, Cancer Research, medicine.medical_specialty, Maximum Tolerated Dose, Population, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Prednisone, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, cardiovascular diseases, education, Survival rate, neoplasms, Response Evaluation Criteria in Solid Tumors, Multiple myeloma, Aged, Aged, 80 and over, education.field_of_study, Bortezomib, business.industry, Hematopoietic Stem Cell Transplantation, Sciences bio-médicales et agricoles, medicine.disease, Carfilzomib, Survival Rate, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Female, Patient Safety, Multiple Myeloma, business, Oligopeptides, Febrile neutropenia, 030215 immunology, medicine.drug
Abstract: Carfilzomib is a novel generation proteasome inhibitor. The Carmysap trial demonstrated that twice-weekly KMP (carfilzomib, melphalan, prednisone) might challenge the MPV (melphalan, prednisone, bortezomib) standard. We sought to study KMP weekly, allowing to increase carfilzomib's dose with maintained efficacy and improved safety profile., info:eu-repo/semantics/published
Published: 2019

30. Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

Author: Bertrand Joly, Hagay Sobol, Isabelle Azais, Hervé Avet-Loiseau, Karine Augeul-Meunier, Catherine Le Bris, Delphine Demangel, Maroulio Pertesi, Xavier Leleu, Maria Victoria Revuelta, Maxime Vallée, Manuel Cliquennois, James D. McKay, Aurore Perrot, Aleksandra Butrym, Matthieu Foll, Björn Nilsson, Javier Oliver, Judit Várkonyi, Emeline Perrial, Xiaomu Wei, Artur Jurczyszyn, Gabriele Buda, Marcin Rymko, Cécile Leyronnas, Robert J. Klein, Elżbieta Iskierka-Jażdżewska, Claire Mathiot, Marzena Wątek, Eric Voog, Olivier Decaux, Florence Desquesnes, Jill Corre, Arnon Nagler, Jean Gabriel Fuzibet, Véronique Dorvaux, Jan Maciej Zaucha, Philippe Rodon, Siwei Chen, Denis Caillot, Laurent Garderet, Michel Maigre, Isabelle Leduc, Fabienne Lesueur, Borhane Slama, Sophie Rigaudeau, Philippe Mineur, Norbert Grząśko, Perrine Galia, Rui Manuel Reis, Federico Canzian, Philippe Helias, Yves-Jean Bignon, Marcin Kruszewski, Victor Moreno, Juan Sainz, Nathalie Cheron, Laurent Voillat, Charles Dumontet, Christian Berthou, Marie Beaumont, Brigitte Pegourie, Etienne Paubelle, Marguerite Vignon, Matteo Pelosini, Philippe Casassus, Isabelle Lambrecht, Laure Vincent, Eileen M Boyle, Annette Juul Vangsted, Pascal Bourquard, Laurent Mosser, Margaret Macro, Gerald Marit, Daniele Campa, Brigitte Kolb, Bruno Royer, Jean Fontan, Ramón García-Sanz, Philippe Moreau, Serge Leyvraz, Malgorzata Krawczyk-Kulis, Krzysztof Jamroziak, Joaquin Martinez-Lopez, Bruno Anglaret, Steven M. Lipkin, Nicole Frenkiel, Ofure Obazee, Marek Dudziński, Pascale Cony-Makhoul, Hervé Naman, Andres Jerez, Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Genetic Cancer Susceptibility, Department of Biological Statistics and Computational Biology, Cornell University, Weill Medical College of Cornell University Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University [New York], Hospices Civils de Lyon (HCL), ProfileXpert, Université de Lyon, LCMT, ProfileXpert, Biomedical Research Institute of Málaga (IBIMA), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), CHU Saint-Antoine [APHP]-Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [APHP], Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7371, INSERM UMR S1146, Laboratoire d'Imagerie Biomédicale, France, parent, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Médecine Interne [CHU Rennes], Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hopital de Périgueux (CH Périgueux), Hopital de Périgueux, Service d'Hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Henri Duffaut (Avignon), Département Oncologie-Hématologie [Charleroi, Belgium], Grand Hôpital de Charleroi [Belgium], Centre Jean Bernard [Le Mans] (Institut Inter-Régional de Cancérologie), CHU de Fort de France (Service Post-Urgences, Pôle RASSUR), CHU de Fort de France, Hôpital JeanMinjoz, Centre hospitalier de Chartres (Chartres) (Service d'Hémato-Oncologie), Service hématologie (CHU d'Amiens), CHU Amiens-Picardie, Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [AP-HP Hôpital Saint-Louis], AP-HP Hôpital Saint-Louis, Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], CHU Saint Louis [APHP], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Médecine Interne [CHU Nice] (Hôpital l'Archet), Hôpital l'Archet-Centre Hospitalier Universitaire de Nice (CHU de Nice), Service d'hématologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier de Valence (Unité d'Hématologie), Centre hospitalier de Valence, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hematology Department - Namur Thrombosis and Hemostasis Center (NTHC), UCL Mont-Godinne, Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CHUV, Lausanne (Departement d'Oncologie), Unité d'Oncologie Médicale, Rodez (Hôpital Jacques Puel, Pôle Medical 2), Unité de coordination en oncogériatrie de Basse-Normandie [Caen] (UCOG Basse-Normandie), CHI Poissy-Saint-Germain, Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, CHG Abbeville (Hématologie), Institut Daniel Hollard [Grenoble], Service d'hématologie et oncologie [Centre Hospitalier de Chalon-sur-Saône William Morey], Centre Hospitalier Chalon-sur-Saône William Morey, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Intergroupe francophone du myélome (IFM), Service d'Onco-Hématologie, Centre Médical de Bligny, Briis sous Forges, Service Hématologie, CH LYON SUD, Pierre benite, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital Sud-Fancilien, CH Sud-Fancilien, Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU de Nîmes), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hématologie, Oncologie Médicale, Centre Azureen de cancérologie, Centre Azureen de cancérologie, Unité d'hématologie et d'oncologie [Centre Hospitalier de Versailles], Centre Hospitalier de Versailles (CHV), Inserm U1035, Biotherapies des Maladies Genetiques et Cancers, Univ Bordeaux, CHU de Bordeaux, Pole de Biologie et Pathologie, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Rhumatologie [Reims], Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), CHU Montpellier, Department of Clinical Hematology, Montpellier, France, Hospitalier et Universitaire de Pointe-à-Pitre (Oncologie Médicale), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CIBER Epidemiologia y Salud Pùblica [Madrid, Spain] (CIBERESP), Instituto de Salud Carlos III (ISC), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], Barretos Cancer Hospital [São Paulo, Brazil], Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary, Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Departement of Hematology, University Hospital, Bydgoszcz, Department of Hematology, Rigshospitalet, Copenhagen, Denmark, Department of Hematology, Jagiellonian University - Medical College, Gdynia Oncology Center, Gdynia and Department of Oncological Propedeutics, Genomic Oncology Area (GENYO), Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Department of Hematology, Insitute of Hematology and Transfusion Medicine, Warsa, Holycross Cancer Center of Kelce, Hematology Clinic, Kielce, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Department of Hematology, Medical University of Lodz, Departement of Experimental Hemato-Oncology, Medical University of Lubli (Polish Myeloma Study Group), Servicio de Hematología, Hospital Universitario 12 de Octubre [Madrid], Hematology and Medical Oncology Department, Hospital Morales Meseguer, Murcia (IMIB), Department of Biology, University of Pisa, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hematology Department, Teaching Hospital No1, Rzeszow, Teaching Hospital N°1, Haematology Department, University Hospital of Salamanca, Hematology Division Chaim Sheba Medical Center, Tel Hashomer, Department of Hematology Copernicus Hospital, Torun, Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Wroclaw Medical University, Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Icahn School of Medicine at Mount Sinai [New York] (MSSM), International Agency for Cancer Research (IACR), INSERM 1052, CNRS 5286, CRCL Lyon, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Centre de Recherche en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UPS), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Charleroi (Hématologie et pathologies de la coagulation), Centre Hospitalier Universitaire de Charleroi, Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Oncologie Génétique, de Prévention et Dépistage, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Département Universitaire Nice (Internal Medicine Department), Hôpital de Nice, Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne-Université Paris 13 (UP13), Laboratoire de diagnostic génétique et moléculaire, Centre Jean Perrin, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU Dijon, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Caen, Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de génomique du myélome [IUCT Oncopole, Toulouse], IUCT Oncopole - Institut Universitaire du Cancer de Toulouse, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CIBER de Epidemiología y Salud Pública (CIBERESP), Biomarkers and Susceptibility Unit, Catalan Institute of Oncology, Molecular Oncology Research Center [São Paulo, Brazil], Centro de Genomica e Investigacion Oncologica (GENYO), Hospital universitario 12 de Octubre, Holycross Cancer Center of Kielce, Hematology Clinic, Department of Laboratory Medicine Lunds University Hospital Lund, Cornell University [New York], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Laboratoire d'Hématologie [CHU Amiens], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier de Versailles André Mignot (CHV), Instituto de Salud Carlos III [Madrid] (ISC), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, Lund University [Lund], Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université catholique de Lille (UCL), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Pisa - Università di Pisa, Mines Paris - PSL (École nationale supérieure des mines de Paris), Wrocław Medical University, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes - Faculté de Médecine (UR Médecine), Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, Letter, [SDV]Life Sciences [q-bio], MEDLINE, Library science, Myeloma, World health, 03 medical and health sciences, 0302 clinical medicine, Multiple myeloma, immune system diseases, Political science, hemic and lymphatic diseases, Exome Sequencing, Genetics, Humans, Exome, Genetic Predisposition to Disease, Cancer genetics, Exome sequencing, Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS, Exosome Multienzyme Ribonuclease Complex, Extramural, Mieloma múltiple, French, Hematology, language.human_language, 3. Good health, Pedigree, [SDV] Life Sciences [q-bio], Exome/genetics, Exosome Multienzyme Ribonuclease Complex/genetics, Female, Genetic Predisposition to Disease/genetics, Germ-Line Mutation/genetics, Multiple Myeloma/genetics, Whole Exome Sequencing/methods, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Donation, language, Multiple Myeloma, Genètica, International agency
Abstract: French National Cancer Institute (INCA) and the Fondation Francaise pour la Recherche contre le Myelome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myelome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myelome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization
Published: 2019

31. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study

Author: Bertrand Arnulf, Lotfi Benboubker, Claire Mathiot, Jérôme J. Lambert, Cécile Sonntag, Pieter Sonneveld, Lixia Pei, Aurore Perrot, Jean Paul Fermand, Karim Belhadj, Pascal Lenain, Matthijs Westerman, Saskia K. Klein, Carla de Boer, William Deraedt, Soraya Wuilleme, Anne-Marie Stoppa, Jessica Vermeulen, Frédérique Orsini-Piocelle, Brigitte Kolb, Jordan M. Schecter, Jean-Pierre Marolleau, Cyrille Hulin, Mark-David Levin, Tobias Kampfenkel, Sen Zhuang, Jill Corre, Christopher Chiu, Jean Fontan, Hervé Avet-Loiseau, Thomas Dejoie, Martine Escoffre-Barbe, Murielle Roussel, Michel Delforge, Jean-Richard Eveillard, Cyrille Touzeau, Lionel Karlin, Tahamtan Ahmadi, Philippe Moreau, Niels W.C.J. van de Donk, Marie C. Béné, Marie-Christiane Vekemans, Sonja Zweegman, Xavier Leleu, Reda Garidi, Hélène Caillon, Mourad Tiab, Margaret Macro, Nathalie Meuleman, Elena Smith, Laurent Garderet, Kon-Siong Jie, Thierry Facon, Denis Caillot, Frédérique Kuhnowski, Annemiek Broijl, Michel Attal, Chantal Doyen, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Site de Recherche Intégrée sur le Cancer - SIRIC « ILIAD » [Nantes] (INCA-DGOS-Inserm), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Universitaire Ziekenhuizen Leuven, Laboratoire de Biochimie [Nantes], CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Hôpital JeanMinjoz, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'Hématologie [Institut Curie], Institut Curie [Paris], Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Caen, Intergroupe francophone du myélome (IFM), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d'hématologie et de biologie [CHU Nantes], Amsterdam UMC - Amsterdam University Medical Center, Service d'Hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Service de Médecine Onco-hématologie [La Roche sur Yon], Centre Hospitalier Universitaire de Nantes, Service clinique des Maladies du Sang, CHU Amiens-Picardie, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service d'hématologie adulte [Hôpital de Saint Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Saint-Quentin, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hematology, CCA - Cancer Treatment and quality of life, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service d'hématologie, and UCL - (SLuc) Service d'hématologie
Subjects: Adult, Male, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, Transplantation, Autologous, Dexamethasone, Drug Administration Schedule, Bortezomib, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, education, Multiple myeloma, education.field_of_study, business.industry, Standard treatment, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, Daratumumab, General Medicine, Middle Aged, medicine.disease, Combined Modality Therapy, Survival Analysis, Thalidomide, Transplantation, Treatment Outcome, Chemotherapy, Adjuvant, Female, Multiple Myeloma, business, medicine.drug
Abstract: Background: Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma. Methods: In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings: Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p
Published: 2019

32. A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma

Author: Loic Ysebaert, Anne Banos, Vincent Delwail, Roch Houot, Nicolas Daguindau, Reda Garidi, Margaret Macro, Ghandi Damaj, Bertrand Joly, Jean Pierre Vilque, Sylvain Carras, Mary Callanan, Fabrice Jardin, Marie Pierre Moles, Magda Alexis, Steven Le Gouill, Emmanuelle Tchernonog, Laurent Voillat, Hacene Zerazhi, Christiane Mounier, J. Fleury, Sandy Amorin, Anne Moreau, Jean Michel Pignon, Adrian Tempescul, Véronique Dorvaux, Yazid Arkam, Luc Fornecker, Caroline Dartigeas, Cecile Chabrot, Philippe Solal Celigny, Pierre Feugier, Remy Gressin, Anna Schmitt, Jean Fontan, Clémentine Sarkozy, Nadine Morineau, Jehan Dupuis, Selim Corm, Krimo Bouadallah, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service d'Hématologie [CH Annecy], CH Annecy, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département de Pathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département d'Hématologie Clinique [CHU Rennes], CHU Pontchaillou [Rennes], Département d’Hématologie Clinique [CHU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service d'hématologie (CH de Dunkerque), Centre Hospitalier Dunkerque, Service Hématologie [CH Métropole Savoie, Chambery], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital de Bayonne, CH de la Côte Basque, Hématologie de liaison avec Institut de Cancérologie de la Loire [CHU de Saint-Etienne], CHU Saint-Etienne, Centre hospitalier universitaire Henri-Mondor [Créteil], Hôpital Universitaire de Caen, Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d’Hématologie [CHU de Clermont Ferrand], Centre Hospitalier Universitaire de Clermont-Ferrand, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d’Hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service hématologie Amiens, CHU Amiens-Picardie, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'hématologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Service d'Hématologie [Bordeaux], Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex-Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Diderot - Paris 7 (UPD7), Hôpital Saint-Quentin, Service d'hématologie et oncologie [Centre Hospitalier de Chalon-sur-Saône William Morey], Centre Hospitalier Chalon-sur-Saône William Morey, Hôpital de Corbeil, Service d'Oncologie médicale [Clinique Victor Hugo], Clinique Victor Hugo, Centre Catherine-de-Sienne [Nantes] (CCS), Département d'Hématologie Clinique [CHU d'Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Médecine Interne Onco-hématologie, Centre Hospitalier Général, Hopital d'Avignon, Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service Hématologie, Mulhouse, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Hématologie Biologique [CHR d'Orléans], Centre Hospitalier Régional d'Orléans (CHR), Service d’Oncologie Hématologique et Thérapie Cellulaire [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [Nantes], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hématologie Clinique [Rennes], Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire d'Hématologie [CHU Amiens], Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional d'Orléans (CHRO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Bendamustine, Male, medicine.medical_specialty, Time Factors, Non-Hodgkin Lymphoma, Lymphoma, Mantle-Cell, Neutropenia, Gastroenterology, Dexamethasone, Disease-Free Survival, Article, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Bendamustine Hydrochloride, Humans, Survival rate, Aged, Aged, 80 and over, business.industry, Hematology, Middle Aged, medicine.disease, Minimal residual disease, 3. Good health, Lymphoma, Survival Rate, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Mantle cell lymphoma, Female, business, 030215 immunology, medicine.drug
Abstract: International audience; We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (P
Published: 2018

33. Development of a quantitative PCR detecting Cunninghamella bertholletiae to help in diagnosing this rare and aggressive mucormycosis

Author: Laurence Millon, Ana Berceanu, Eric Deconinck, Benoît Valot, Emeline Scherer, Nicolas Belin, Jean Fontan, Adrien Chauchet, Anne-Pauline Bellanger, Jean-Christophe Navellou, Steffi Rocchi, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Service de parasitologie et mycologie [CHU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Service de réanimation médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Service de Réanimation médicale [CHRU Besançon]
Subjects: 0301 basic medicine, Male, Posaconazole, medicine.medical_specialty, Antifungal Agents, Chronic lymphocytic leukemia, 030106 microbiology, Real-Time Polymerase Chain Reaction, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Fatal Outcome, Internal medicine, Medicine, Humans, Mucormycosis, 030212 general & internal medicine, Lung, Cunninghamella, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Transplantation, Hematology, biology, business.industry, Aplasia, medicine.disease, biology.organism_classification, Dermatology, Cunninghamella bertholletiae, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Leukemia, business, medicine.drug
Abstract: International audience; Mucormycosis is an invasive mold infection, frequently fatal in immunocompromised patients. We report the case of a patient with chronic lymphocytic leukemia admitted to the hematology unit for febrile aplasia. Pulmonary lesions suggesting a fungal infection expanded/increased despite a combination of posaconazole and liposomal amphotericin B. The fungal biomarkers performed repeatedly were negative. At D65 after chemotherapy a bronchial biopsy was positive for Cunninghamella bertholletiae. The patient died despite appropriate antifungal management. A qPCR targeting Cunninghamella was developed a posteriori, and a retrospective analysis showed that a sample was positive more than 30 days before culture-based identification could be made.
Published: 2018

34. MIROIR: 4-Year Interim Analysis of a Multicenter, Non-Interventional Study in France of Pomalidomide in Relapsed or Refractory Multiple Myeloma

Author: Jean Fontan, Arnaud Jaccard, Laure Vincent, Olivier Decaux, Xavier Leleu, Florence Lachenal, Sophie Gourgou, Lionel Karlin, Bertrand Arnulf, Aurore Perrot, Cécile Fohrer, Mohamad Mohty, Anne-Marie Stoppa, Sylvain Choquet, Cyrille Hulin, Philippe Moreau, Caroline Bureau Lenoir, Denis Caillot, Margaret Macro, and Jean-Richard Eveillard
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, Refractory Multiple Myeloma, Hematology, Interim analysis, Pomalidomide, Internal medicine, Non interventional, medicine, business, medicine.drug
Published: 2019

35. Four-Year Interim Analysis of Miroir, a French Multicenter, Non-Interventional Study of Pomalidomide in Relapsed/Refractory Multiple Myeloma

Author: Bertrand Arnulf, Anne-Marie Stoppa, Xavier Leleu, Florence Lachenal, Jean Fontan, Lionel Karlin, Laure Vincent, Mohamad Mohty, Cécile Fohrer, Choquet Sylvain, Philippe Moreau, Jean-Richard Eveillard, Aurore Perrot, Cyrille Hulin, Margaret Macro, Caroline Bureau Lenoir, Sophie Gourgou, Denis Caillot, Arnaud Jaccard, and Olivier Decaux
Subjects: education.field_of_study, medicine.medical_specialty, Adult patients, business.industry, Immunology, Population, Cell Biology, Hematology, medicine.disease, Interim analysis, Pomalidomide, Biochemistry, Internal medicine, Relapsed refractory, Non interventional, medicine, Overall survival, business, education, Multiple myeloma, medicine.drug
Abstract: BACKGROUND Real-world data on the use of pomalidomide (POM) for the treatment (Tx) of relapsed/refractory multiple myeloma (RRMM) are limited. The MIROIR study was designed to evaluate POM Tx in routine clinical practice in France. Here, we present results from a prespecified 4-year interim analysis. METHODS MIROIR is a multicenter, observational, ambispective, non-interventional study of POM in routine clinical practice. Adult patients (pts) with MM who initiated POM Tx in France between October 1, 2014, and September 30, 2018, were included. All pts were required to be enrolled in the French IMNOVID® registry. Data were collected from medical records of consenting pts. Key exclusion criteria included previous treatment with POM or simultaneous participation in a clinical trial. The primary endpoint is progression-free survival (PFS) at 6 months. Key secondary endpoints include time to next Tx (TTNT), overall survival (OS), and safety. This study is ongoing; targeted enrollment is 3000 pts (ClinicalTrials.gov, NCT02902900). RESULTS A total of 2099 pts were included in this analysis (median follow-up: 23.3 months; data cutoff: February 1, 2019). Median age was 70.0 years, and 655 pts (31.2%) were aged ≥ 75 years; 1134 pts (54.0%) were male. Median time from start of first-line Tx to POM initiation was 51.4 months. Pts had received a median of 3 prior lines of therapy (range: 0-9), with 914 (43.5%), 644 (30.7%), 312 (14.9%) and 229 pts (10.9%) receiving ≤ 2, 3, 4, and ≥ 5 prior lines, respectively. From 2014 to 2016, the median number of prior lines of therapy before POM initiation was 3, and from 2016 to 2018, the median was 2. Nearly all pts received prior lenalidomide (LEN; 97.0%) and bortezomib (96.7%). POM was initiated at 4 mg/day in 1635 pts (77.9%) overall and in 1216 pts (84.2%) aged < 75 years and in 419 pts (64.0%) aged ≥ 75 years. Dexamethasone was prescribed at 20 mg/day and 40 mg/day in 507 (35.1%) and 732 pts (50.7%) aged < 75 years and in 405 (61.8%) and 62 pts (9.5%) aged ≥ 75 years. Overall, the 6-month PFS rate was 51.7% (95% CI, 49.4%-54.1%). Other key PFS data in pt subgroups are reported in the Table. In the overall population, median TTNT, 12-month OS rate, and median OS were 10.4 months (95% CI, 9.7-11.2), 70.6% (95% CI, 68.5-72.6), and 24.6 months (95% CI, 22.9-not reached), respectively. Among 1164 pts (55.5%) with ≥ 1 adverse event (AE), the most common AEs were neutropenia (290 pts; 24.9%), infections (263 pts; 22.6%), thrombocytopenia (99 pts; 8.5%), and asthenia (87 pts; 7.5%). POM dose was reduced due to an AE in 20.7% of pts; POM Tx was interrupted or discontinued due to an AE in 36.2% and 15.2% of pts, respectively. CONCLUSIONS The results of this interim analysis confirm the efficacy of POM reported in clinical trials and underscore its role in Tx of RRMM, including after LEN Tx. Median PFS in pts with ≤ 2 prior Tx lines was numerically longer than in pts who had more Tx lines, supporting earlier Tx with POM. PFS outcomes were similar regardless of the duration of LEN Tx (< or ≥ 6 months) before initiation of POM and whether pts had received LEN or another Tx as their most recent therapy. The latter finding suggests that POM can be used after relapse or resistance to LEN and that there is no need to replace an IMiD agent with another class of treatment. Disclosures Decaux: Celgene Corporation, Janssen, Takeda, Amgen: Honoraria. Macro:Celgene, Janssen, Amgen, Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial Support. Gourgou:Celgene: Employment, Equity Ownership. Lachenal:Celgene: Other: Scientific Comittee's. Stoppa:Celgene: Honoraria. Jaccard:Abbvie: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Perrot:jannsen: Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Karlin:AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fohrer:Celgene: Consultancy, Honoraria. Leleu:Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Hulin:celgene: Consultancy, Honoraria; Janssen, AbbVie, Celgene, Amgen: Honoraria.
Published: 2019

36. A Prospective Phase II Trial of Lenalidomide and Dexamethasone in POEMS Syndrome

Author: Arnaud Jaccard, Lionel Karlin, Benjamin Hebraud, Laurent Frenzel, Sylvain Choquet, Mohamad Mohty, Mamoun Dib, Laure Vincent, Borhane Slama, Lionel Galicier, Olivier Tournilhac, Karim Belhadj-Merzoug, Philippe Moreau, Olivier Decaux, Lofti Benboubker, Denis Caillot, Jean Fontan, Hervé Maisonneuve, Sebastien Bender, Lucile Musset, and Jean-Paul Fermand
Subjects: Cancer Research, Oncology, Hematology
Published: 2019

37. High response rate and acceptable toxicity of a combination of rituximab, vinorelbine, ifosfamide, mitoxantrone and prednisone for the treatment of diffuse large B-cell lymphoma in first relapse: results of the R-NIMP GOELAMS study

Author: Anne Banos, Aline Schmidt-Tanguy, Thierry Lamy, Steven Le Gouill, Emmanuel Gyan, Stéphane Courby, Olivier Tournilhac, Philippe Solal-Celigny, Kamel Laribi, Delphine Senecal, Jean Fontan, Diane Damotte, Guillaume Cartron, Philippe Quittet, Hervé Maisonneuve, Remy Gressin, François Dreyfus, Nina Arakelyan, and Magda Alexis
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Phases of clinical research, Vinblastine, Vinorelbine, Gastroenterology, Antibodies, Monoclonal, Murine-Derived, Recurrence, Prednisone, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Ifosfamide, Aged, Chemotherapy, Mitoxantrone, business.industry, Hematology, Middle Aged, medicine.disease, Combined Modality Therapy, Survival Analysis, Surgery, Female, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, Stem Cell Transplantation, medicine.drug
Abstract: Summary The optimal management of relapsed diffuse large B-cell lymphoma (DLBCL) is not standardized. The Groupe Ouest Est des Leucet aAutres Maladies du Sang developed a combination of vinorelbine, ifosfa- mide, mitoxantrone and prednisone (NIMP) for the treatment of relapsed DLBCL, and assessed its efficacy and safety in association with rituximab (R). This multicentric phase II study included 50 patients with DLBCL in first relapse, aged 18-75 years. Patients received rituximab 375 mg/m² day 1, ifosfamide 1000 mg/m² days 1-5, vinorelbine 25 mg/m² days 1 and 15, mitoxantrone 10 mg/m² day 1, and prednisone 1 mg/kg days 1-5, every 28 days for three cycles. Responding patients underwent autologous trans- plantation or received three additional R-NIMP cycles. All patients were evaluable for toxicity and 49 for response. Centralized pathology review confirmed DLBCL in all cases. Toxicities were mainly haematological with infectious events needing hospitalization in nine cases. Two toxic deaths were observed. After three cycles, 22 patients (44%) achieved complete response/unconfirmed complete response, 11 achieved partial response (24%), 2 had stable disease and 13 progressed. The non-germinal centre B immunophenotype was associated with shorter progression-free survival. in conclusion, the R-NIMP regimen displayed significant activity in relapsed DLBCL, with acceptable toxicity and should be considered a candidate for combination with new agents.
Published: 2013

38. Upfront autologous stem cell transplantation for newly diagnosed elderly multiple myeloma patients: a prospective multicenter study

Author: Anne-Marie Stoppa, Lionel Karlin, Mor Seny Gueye, Laurent Garderet, Jean Fontan, Marie Lorraine Chretien, Souhila Ikhlef, Mohamad Mohty, Denis Caillot, Cyrille Touzeau, Didier Blaise, Philippe Moreau, Emmanuelle Polge, Zora Marjanovic, Myriam Labopin, Eric Beohou, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Society for Blood and Marrow Transplantation (EBMT), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôtel-Dieu de Nantes, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HAL UPMC, Gestionnaire, CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Melphalan, Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Transplantation Conditioning, medicine.medical_treatment, Hematopoietic stem cell transplantation, Article, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Internal medicine, Humans, Medicine, Prospective Studies, Autografts, Multiple myeloma, Aged, Lenalidomide, Aged, 80 and over, Peripheral Blood Stem Cell Transplantation, business.industry, Plerixafor, Remission Induction, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Induction Chemotherapy, Hematology, medicine.disease, Survival Analysis, 3. Good health, Surgery, Consolidation Chemotherapy, Transplantation, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, business, 030215 immunology, medicine.drug
Abstract: The feasibility and efficacy of high-dose melphalan followed by autologous hematopoietic stem cell transplantation in newly diagnosed elderly patients with multiple myeloma was analyzed prospectively. Fifty-six multiple myeloma patients, aged 65 years or over, from 6 French centers were studied. The induction therapy was bortezomib-based in combination with dexamethasone and either thalidomide, cyclophosphamide or lenalidomide, for 4-6 cycles. Peripheral blood stem cells were collected after high-dose cyclophosphamide plus G-CSF or G-CSF alone, with plerixafor if needed. The conditioning regimen consisted of melphalan at 140 mg/m2 in 18 patients (36%) and 200 mg/m2 in 32 (64%). Three months post autologous hematopoietic stem cell transplantation, a 2-month consolidation phase with either lenalidomide plus dexamethasone or bortezomib-based combination therapy was allowed, but maintenance treatment was not given. All but 6 patients underwent autologous hematopoietic stem cell transplantation and 3 had tandem transplantations. The treatment-related mortality was 0% at 100 days post transplantation. Sixty-eight percent received consolidation therapy following transplantation. The best response achieved was 40% complete response, 36% very good partial response, and 18% partial response. After a median follow up of 21 months (range 6-31), the estimated progression-free and overall survival rates at two years were 76% [95%CI: (61.6-94.1)] and 88% [95%CI: (76.7-100)], respectively. The higher dose of melphalan (200 mg/m2) afforded superior progression-free and overall survival rates. This prospective study provides evidence for the safety and efficacy of autologous hematopoietic stem cell transplantation as a first-line treatment approach in elderly multiple myeloma patients. (clinicaltrials.gov identifier: 01671826).
Published: 2016

39. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial

Author: Mathieu Puyade, Karim Belhadj, Brigitte Kolb, Carla Araujo, Arnaud Jaccard, Michel Attal, Odile Luycx, Thomas Dejoie, Bruno Royer, Laurent Garderet, Sylvie Glaisner, Pascal Lenain, Denis Caillot, Anne-Marie Stoppa, Karim Laribi, Hélène Caillon, Jean-Claude Eisenmann, Hervé Avet-Loiseau, Lucie Planche, Pascal Godmer, Jean-Paul Fermand, Philippe Rodon, Murielle Roussel, Marc Wetterwald, Jean-Valère Malfuson, Gerald Marit, Martine Escoffre, Laetitia Biron, Philippe Moreau, Mamoun Dib, Jean Fontan, Thierry Facon, Driss Chaoui, Brigitte Pegourie, Carine Chaleteix, Borhane Slama, Cyrille Hulin, Mourad Tiab, Sabine Brechignac, Margaret Macro, Olivier Allangba, and Véronique Dorvaux
Subjects: Adult, Male, endocrine system, medicine.medical_specialty, Neutropenia, Immunology, Urology, Biochemistry, Dexamethasone, law.invention, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Randomized controlled trial, law, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Medicine, Humans, Prospective Studies, Prospective cohort study, Cyclophosphamide, Multiple myeloma, Aged, business.industry, Anemia, Cell Biology, Hematology, Middle Aged, medicine.disease, Thrombocytopenia, Surgery, Thalidomide, 030220 oncology & carcinogenesis, Female, business, Multiple Myeloma, 030215 immunology, medicine.drug
Abstract: The Intergroupe Francophone du Myelome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamide-dexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56.2% in the VCD arm (P = .05). In addition, the overall response rate was significantly higher in the VTD arm (92.3% vs 83.4% in the VCD arm; P = .01). Hematologic toxicity was higher in the VCD arm, with significantly increased rates of grade 3 and 4 anemia, thrombocytopenia, and neutropenia. On the other hand, the rate of peripheral neuropathy (PN) was significantly higher in the VTD arm. With the exception of hematologic adverse events and PN, other grade 3 or 4 toxicities were rare, with no significant differences between the VTD and VCD arms. Our data support the preferential use of VTD rather than VCD in preparation for ASCT. This trial was registered at www.clinicaltrials.gov as #NCT01564537 and at EudraCT as #2013-003174-27.
Published: 2016

40. Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Author: Brigitte Kolb, Simona Iacobelli, Roman Hájek, Carine Chaleteix, Norbert Claude Gorin, Jean Luc Harousseau, Francesco Onida, Mohamad Mohty, Gösta Gahrton, Dietger Niederwieser, Philippe Moreau, Philippe Casassus, Heinz Ludwig, Ingrid Lafon, Bernd Hertenstein, Brigitte Pegourie, Andrew Cakana, Mauricette Michallet, Nicolas Ketterer, Alois Gratwohl, Marleen van Os, Mamoun Dib, Jean Fontan, Giuseppe Milone, Chantal Doyen, Curly Morris, Tamas Masszi, Laurent Garderet, Christian Koenecke, and Theo de Witte
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Transplantation, Autologous, Gastroenterology, Dexamethasone, Disease-Free Survival, Drug Administration Schedule, Settore MED/01 - Statistica Medica, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Autologous transplantation, Survival rate, Multiple myeloma, Aged, business.industry, Hazard ratio, Translational research Immune Regulation [ONCOL 3], Middle Aged, medicine.disease, Boronic Acids, Thalidomide, 3. Good health, Surgery, Transplantation, Treatment Outcome, Oncology, Pyrazines, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, business, Stem Cell Transplantation, 030215 immunology, medicine.drug
Abstract: Purpose This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT). Patients and Methods Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m2 intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months). Results Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v 13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 21%; P = .001), and the median duration of response was longer (17.9 v 13.4 months; P = .04). The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia. Conclusion VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.
Published: 2012

41. Carfilzomib Weekly Plus Melphalan and Prednisone in Newly Diagnosed Elderly Multiple Myeloma (IFM 2012-03)

Author: Mourad Tiab, Xavier Leleu, Pascal Bourquard, Philippe Moreau, Laurent Voillat, Brigitte Kolb, Jean Fontan, Arnaud Jaccard, Marie-Odile Petillon, Thierry de Revel, Olivier Decaux, Philippe Rodon, Anna Schmitt, Jean Claude Eisenmann, Frédérique Kuhnowski, Véronique Dorvaux, Nathalie Meuleman, Gérard Lepeu, Damien roos Weil, Marie-Lorraine Chretien, Murielle Roussel, Olivier Fitoussi, Karim Belhadj-Merzoug, Michel Attal, Sophie Cereja, Thierry Facon, Catherine Humbrecht-Kraut, Lionel Karlin, Fritz Offner, Carla Araujo, Eric Voog, Jamile Frayfer, Pascal Lenain, Cyrille Hulin, Sophie Rigaudeau, Service d'Hématologie, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Hôpital Général de La Roche sur Yon, CRLCC Henri Becquerel, CHU Pontchaillou [Rennes], Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre hospitalier d'Avignon, CH Avignon, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Centre Hospitalier Chalon-sur-Saône William Morey, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier de Meaux, Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), Hôpital Universitaire de Vandoeuvre les Nancy, Laboratoire d'Hématologie [Rangueil], Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital de Rangueil, Service d'Hématologie Clinique, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Hôpital Claude Huriez, and Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille )
Subjects: Melphalan, Cancer Research, medicine.medical_specialty, [ SDV ] Life Sciences [q-bio], business.industry, Immunology, Cell Biology, Hematology, Newly diagnosed, medicine.disease, Biochemistry, Pulmonary hypertension, Carfilzomib, chemistry.chemical_compound, Peripheral neuropathy, Oncology, chemistry, Prednisone, Internal medicine, medicine, business, Intensive care medicine, Multiple myeloma, Febrile neutropenia, medicine.drug
Abstract: Background. New standards with increasing efficacy that are also characterized with improving the quality of life are needed for elderly myeloma patients. Although MPT and MPV regimens are remarkable in terms of efficacy, quality of life while on treatment with these 2 regimens remain an issue. The Carmysap twice weekly carfilzomib-based phase 2 study has demonstrated that Carfilzomib at the MTD of 36mg/m² might challenge bortezomib in the VMP standard. However, it has become routine practice to use bortezomib on a weekly schedule, with maintained efficacy and an improved safety profile. We sought to demonstrate that Carfilzomib Weekly plus Melphalan and Prednisone will prove strongly efficacious with acceptable safety profile and quality of life to newly diagnosed elderly multiple myeloma (eNDMM). Methods . IFM2012-03 (also called carmysap weekly) is a phase 1/2 multicenter open label single arm study to determine MTD during the phase 1 part and VGPR+CR rate during the phase 2 part of the study. The inclusion/exclusion criteria of interest were eNDMM (65 and older), with symptomatic and measurable disease, with absolute neutrophils ≥1 G/L, untransfused platelet count ≥75 G/L, hemoglobine ≥8.5 g/dL and clairance creatinine ≥ 30ml/min. We report herein the phase 1 part of the study which last cohort was completed at ASH abstract deadline. For the phase 1 part of the study, each cohort was 6 patients based, and started at 36mg/m² of carfilzomib on days 1, 8, 15, 22 using IV, 30 minutes infusion, route followed by a 13-day rest period per 35-days cycles, melphalan given at 0.25mg/kg/j and oral prednisone 60mg/m², both on days 1 to 4. The subsequent cohorts' doses for carfilzomib were 45, then 56 and finally 70mg/m². 9 cycles were planned as induction followed by a maintenance phase of weekly carfilzomib monotherapy given at 36mg/m² weekly for one year. The MTD was determined when ˃2 DLTs were observed. DLTs were considered during cycle 1 if any hematologic toxicity of grade 4 intensity or preventing administration of 2 or more of the 4 carfilzomib doses of the first treatment cycle, grade ≥3 febrile neutropenia, grade ≥3 gastrointestinal toxicities, any other grade ≥3 nonhematologic toxicity considered related to CMP by the principal investigator, grade ≥ 3 peripheral neuropathy persisting for more than 3 weeks after discontinuation of study drugs. Results. 26 NDMM patients recruited, 24 treated in the study, 6 per cohort at 36 mg/m² carfilzomib +MP, then 45 then 56, and finally at 70mg/m² which cohort cycle 1 is up and running. The median age was 74 with 10 patients older than 75 and sex ratio M/F 65. There was a DLT at 36 mg/m² carfilzomib (grade 4 lymphopenia), one at 45 (lysis syndrome complicated with grade 4 renal insufficiency, two at 56 (cardiac insufficiency grade 3 and febrile neutropenia grade 3). At ASH deadline, all patients from cohort 36 of carfilzomib have completed induction and maintenance up to cycle 6, 5/6 of cohort 45 have completed induction and started the maintenance phase, 5/6 of cohort 56 have completed cycle 6 of induction and pursue within the induction phase, and finally all patients from cohort 70 of carfilzomib are undergoing cycle 1. There are 22 SAE reported for a total of 171 cycles administered of carfilzomib +MP. So far, 3 patients (out of 24) have stopped treatment, including the 2 patients with DLTs, lysis syndrome and cardiac failure, and one patient that presented with pulmonary hypertension later in the disease course on cycle 5 of the 56mg/m² carfilzomib +MP cohort. And, an extra 3 patients have had Carfilzomib dose reduction, 2 patients at 36 from 45 and one at 45 from 56, for neutropenia grade 4, thrombocytopenia grade 4, and Dyspnea grade 3, respectively. Conclusion. The MTD of weekly carfilzomib in the combination to Melphalan and Prednisone could be determined at 70mg/m² in elderly NDMM, demonstrating the good safety profile of carfilzomib in this regimen and fragile population. The complete dataset of the entire study will be updated at ASH with response rate, survival and safety profile. Disclosures Leleu: Chugai: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; BMS: Honoraria; Novartis: Honoraria; TEVA: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Karlin:Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria. Fitoussi:Sandoz: Membership on an entity's Board of Directors or advisory committees. Moreau:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Published: 2015

42. Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial

Author: Hervé Avet-Loiseau, Jean-Luc Harousseau, Brigitte Kolb, Thierry Facon, Catherine Sebban, Mamoun Dib, Jean Fontan, Claire Mathiot, Michel Attal, Chantal Doyen, Dixie Lee Esseltine, Laurent Voillat, Jean-Gabriel Fuzibet, Brigitte Pegourie, Philippe Moreau, Bernard Grosbois, Anne-Marie Stoppa, Carine Chaleteix, Cyrille Hulin, Laurent Garderet, Lucie Planche, Jérôme Jaubert, and Nicolas Ketterer
Subjects: Adult, Oncology, medicine.medical_specialty, Time Factors, Multivariate analysis, Immunology, Biochemistry, Disease-Free Survival, law.invention, Autologous stem-cell transplantation, Randomized controlled trial, law, Internal medicine, medicine, Humans, Very Good Partial Response, Intention-to-treat analysis, Hematology, Bortezomib, business.industry, Remission Induction, Cell Biology, Middle Aged, Prognosis, Intention to Treat Analysis, Surgery, Clinical trial, Treatment Outcome, Multiple Myeloma, business, medicine.drug
Abstract: In the 2005-01 trial, we have demonstrated that bortezomib-dexamethasone as induction therapy before autologous stem cell transplantation was superior to vincristine-adriamycin-dexamethasone. We conducted a post-hoc analysis to assess the prognostic impact of initial characteristics as well as response to therapy in patients enrolled in this study. Multivariate analysis showed that ISS stages 2 and 3 and achievement of response less than very good partial response (VGPR) both after induction therapy and after autologous stem cell transplantation were adverse prognostic factors for progression-free survival, the most important one being achievement of response less than VGPR after induction. Progression-free survival was significantly improved with bortezomib-dexamethasone induction therapy in patients with poor-risk cytogenetics and ISS stages 2 and 3 compared with vincristine-adriamycin-dexamethasone. In these 2 groups of patients, achievement of at least VGPR after induction was of major importance. This study is registered with EudraCT (https://eudract.ema.europa.eu; EUDRACT 2005-000537-38) and http://clinicaltrials.gov (NCT00200681).
Published: 2011

43. Light Chain Escape in Multiple Myeloma

Author: Jean Luc Harousseau, Benjamin Hebraud, Philippe Moreau, Brigitte Kolb, Anna Schmitt, Frédérique Kuhnowski, Michel Attal, Mourad Tiab, Sophie Cereja, Claire Mathiot, Pascal Bourquard, Thomas Dejoie, Philippe Rodon, Jean Fontan, Guillemette Fouquet, Brigitte Pegourie, Jean Claude Eisenmann, Catherine Humbrecht-Kraut, Denis Caillot, Hervé Avet-Loiseau, Laurent Garderet, Murielle Roussel, Damien Roos-Weil, Lionel Karlin, Olivier Decaux, Thierry Facon, Gérard Lepeu, Sophie Rigaudeau, Jean-Paul Fermand, Karim Belhadj, Arnaud Jaccard, Cyrille Hulin, Carla Araujo, Eric Voog, Jamile Frayfer, Pascal Lenain, Jean Valère Malfuson, Véronique Dorvaux, Nathalie Meuleman, Xavier Leleu, Laurent Voillat, and Marie Lorraine Chretien
Subjects: business.industry, Steering committee, Immunology, Cell Biology, Hematology, Missed diagnosis, Biochemistry, Management, Serum free, Median time, Large study, Standard test, Medicine, In real life, business
Abstract: Background. Progression by serum free light chain (sFLC) test without or preceding progression with intact immunoglobulin (Ig) is called light chain escape. This event alone is not considered a progression for patients with Multiple Myeloma (MM) according to International guidelines, although it is often considered a progression in real life and by clinical trials' investigators. We therefore sought to determine whether light chain escape would be a predictor of relapse and thus question a possible need to modify the current criteria for progression according to the International Myeloma Working Group (IMWG). Material and method. We have reviewed 325 (323 for analysis) patients that presented with a progression in the IFM/DFCI2009 phase 3 study (Attal et al. NEJM 2017). Among these 323 patients, 260 had initial tumor bulk measurement with intact Ig by serum protein electrophoresis test (SPEP; Ig ≥ 10 g/L) and 63 light chain MM (Ig < 10 g/L) measured using urine protein electrophoresis (UPEP). All progressions were validated in the central laboratory of CHU de Nantes (Dr T. Dejoie) and followed IMWG recommendations. sFLC increase was determined by absolute increase ≥ 100 mg/L and ≥ 25% from nadir value of the difference between involved and uninvolved FLC (ΔiFLC). Light chain escape was defined as sFLC increase without progression by SPEP (Ig increase ≥ 5 g/L and ≥ 25%) or UPEP (increase ≥ 200 mg/24h and ≥ 25%). Results. Among the 260 patients with intact Ig at diagnosis, 3 (1.15%) patients presented a light chain escape: progression by sFLC test without progression by SPEP. In parallel, 228 patients (87.7%) progressed by SPEP, of whom 18/228 (6.25%) showed a sFLC increase preceding the increase of intact Ig, with a median delay of 63 days. Among the 63 light chain MM, 6 (9.5%) patients presented a light chain escape: progression by sFLC test without progression by UPEP. Interestingly, 6 other patients (9.5%) progressed by SPEP even though Ig was < 10 g/L at diagnosis. Of the remaining 46 patients, 38 (60.3%) showed sFLC increase before progression by UPEP. Finally, 8 patients (12.7%) progressed but with intact Ig pauci-secreting MM meeting none of the M spike based progression criteria. Median time from iFLC nadir to ΔiFLC ≥ 100 mg/L was 280 days for light chain MM, 496 days for intact Ig MM, and 651 days for light chain escape. Median time from ΔiFLC ≥ 100 mg/L to follow-up visit to assess progression was 402 days light chain MM, 536 days for intact Ig MM, and 713 days for light chain escape. Overall, 9 (3%) patients had true light chain escape with progression by sFLC test without any other progression criteria. In parallel, in 56 (17%) patients, sFLC increase preceded progression to MM by standard test (SPEP or UPEP). Still the vast majority of patients had a regular relapse using the standard markers for progression. Conclusion. Based on a large study of patients treated into a phase 3 clinical trial with centralized assessment of response and progression, we showed that 20% of patients had progression by sFLC without meeting standard progression markers, of whom 3% had true light chain escape and 17% early light chain increase. Even though true light chain escape seems to be a rare phenomenon, analysis of sFLC test could help to avoid delayed or missed diagnosis of progression in 20% of patients in this clinical trial. This data should be confirmed in another database to assess whether a modification in the progression criteria in MM International guidelines should be proposed. Disclosures Hulin: Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Roussel:Amgen: Consultancy; Celgene: Consultancy; Takeda: Consultancy. Hebraud:Amgen: Consultancy; Janssen: Consultancy, Other: Lecture fees; travel and accommodation for congress, Research Funding; Sanofi: Consultancy; Takeda: Consultancy; Celgene: Consultancy, Other: Lecture fees, Research Funding. Karlin:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Belhadj:Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Decaux:Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Garderet:Amgen: Consultancy; Takeda: Consultancy; Celgene: Consultancy. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Avet-Loiseau:Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Moreau:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Attal:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janseen: Consultancy, Research Funding; Sanofi: Consultancy. Leleu:Karyopharm: Honoraria; Gilead: Honoraria; Incyte: Honoraria, Other: steering committee membership ; Roche: Honoraria; Sanofi: Honoraria, Other: steering committee membership steering committee membership ; Novartis: Honoraria, Other: steering committee membership ; Amgen: Honoraria, Other: steering committee membership ; Merk: Honoraria, Other: steering committee membership ; Takeda: Honoraria, Other: steering committee membership ; BMS: Honoraria, Other: steering committee membership ; Celgene: Honoraria, Other: steering committee membership ; Janssen: Honoraria, Other.
Published: 2018

44. A National, Multicenter, Non-Interventional Study of Pomalidomide in Relapsed/Refractory Multiple Myeloma: Updated Results from the Miroir Study

Author: Jean-Richard Eveillard, Lionel Karlin, Anne-Marie Stoppa, Jean Fontan, Arnaud Jaccard, Mohamad Mohty, Choquet Sylvain, Margaret Macro, Aurore Perrot, Cécile Fohrer, Olivier Decaux, Denis Caillot, Cyrille Hulin, Laure Vincent, Sophie Gourgou, Caroline Bureau Lenoir, Xavier Leleu, Florence Lachenal, Philippe Moreau, and Bertrand Arnulf
Subjects: medicine.medical_specialty, business.industry, Immunology, Authorization, Cell Biology, Hematology, Time to next treatment, Pomalidomide, Biochemistry, Family medicine, Relapsed refractory, Non interventional, Medicine, In patient, Immunomodulatory Agent, business, health care economics and organizations, After treatment, medicine.drug
Abstract: BACKGROUND Pomalidomide (POM; Imnovid) in combination with low-dose dexamethasone (LoDex) demonstrated a significant improvement in progression-free survival (PFS; median, 4.0 vs 1.9 months; P < .0001) and overall survival (OS; median, 12.7 vs 8.1 months; P = .0285) vs high-dose dexamethasone in a phase 3 study of patients with relapsed/refractory multiple myeloma (RRMM; MM-003; San Miguel et al. Lancet Oncol. 2013;14:1055-1066). This trial led to the European approval of POM + LoDEX in patients with RRMM previously treated with ≥ 2 regimens, including lenalidomide (LEN) and bortezomib (BORT), and who had disease progression on their last therapy. However, data on the use of POM in the real-world setting are limited. The goal of the MIROIR study is to investigate the usage, efficacy, and tolerability of POM in current clinical practice in France. Results from a pre-specified 3-year interim analysis are presented. METHODS MIROIR is a multicenter, non-interventional study of POM in routine clinical practice. Adults (aged ≥ 18 years) with multiple myeloma who initiated POM treatment in France between October 1, 2014, and September 30, 2017, were included (data cutoff, February 1, 2018). All patients were required to be enrolled in the Imnovid registry (a non-interventional post-marketing authorization registry) and to provide consent. Key exclusion criteria included previous treatment with POM or simultaneous participation in a clinical trial. Patients were followed up for ≤ 24 months after treatment initiation. Data were collected from patient medical files. The primary endpoint is PFS at 6 months. PFS is defined as the time from POM treatment initiation to the first progression according to International Myeloma Working Group criteria or death from any cause. Key secondary endpoints include OS, time to next treatment (TTNT), and safety. This study is ongoing; targeted enrollment is 3000 patients (ClinicalTrials.gov, NCT02902900). RESULTS A total of 1581 patients were included in this analysis (median follow-up, 19.1 months). The median age was 69.8 years, and 480 patients (30.4%) were aged ≥ 75 years; 844 patients (53.4%) were male. The median time from first-line treatment to POM initiation was 52.6 months. Patients had received a median of 3 prior lines of therapy (range, 0-9), with 628 (39.7%), 509 (32.2%), and 444 patients (28.1%) receiving ≤ 2, 3, and ≥ 4 prior lines, respectively. The most common prior treatments included BORT (97.3%), LEN (97.0%), melphalan (80.3%), and autologous/allogeneic stem cell transplant (50.0%). POM was prescribed at 4 mg/day in 923 patients (83.8%) aged < 75 years and in 300 patients (62.5%) aged ≥ 75 years. Dexamethasone was prescribed at 20 mg/day and 40 mg/day in 382 (34.7%) and 566 patients (51.4%) aged < 75 years and at 20 mg/day and 40 mg/day in 287 (59.8%) and 49 patients (10.2%) aged ≥ 75 years. The 6-month PFS rate was 50.5% (95% CI, 47.7%-53.3%). Other key PFS data are reported in the Table. Median TTNT was 9.8 months (95% CI, 9.0-10.6 months). The 12-month OS rate was 68.7% (95% CI, 66.1%-71.0%), with a median OS of 22.4 months (95% CI, 21.0-24.6 months). A total of 233 serious adverse events (AEs) related to POM were reported; 26 (11.2%) were neutropenia, 13 (5.6%) were pancytopenia, and 13 (5.6%) were thrombocytopenia. POM dose was reduced due to an AE in 20.0% of patients; treatment was discontinued or interrupted due to an AE in 14.9% and 35.2% of patients, respectively. Many patients received concomitant treatments and supportive care in the form of thromboprophylaxis (81.2%), antiviral prophylaxis with valacyclovir (63.3%), antibiotic prophylaxis (55.8%), bisphosphonates (20.9%), erythropoietin (20.1%), and granulocyte colony-stimulating factor (8.8%). CONCLUSIONS The results of this interim analysis of the real-world MIROIR study confirm the efficacy of POM reported in clinical trials and underscore its role as a treatment in RRMM. Median PFS was numerically longer in patients who had received only 1 to 2 prior lines of therapy, supporting earlier initiation of POM. The results also indicate that POM is effective in patients whose disease has relapsed or developed resistance to LEN; PFS outcomes were similar regardless of whether patients had received LEN or another treatment as their most recent therapy. This suggests that there is no need to switch from an immunomodulatory agent to another class of treatment after relapse or resistance to LEN. Disclosures Hulin: Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Macro:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress. Gourgou:Roche: Other: Expertise methodological seminar Force 1 since 2007 and real-life study ; Celgene Corporation: Other: Expertise methodological mirror . Lachenal:Celgene: Other: Scientific Committees . Stoppa:Celgene Corporation: Honoraria. Moreau:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Perrot:Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Mohty:MaaT Pharma: Consultancy, Honoraria. Karlin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Fohrer:Celgene: Consultancy, Honoraria. Sylvain:Gilead: Other: scientific advisor board. Leleu:Celgene: Honoraria, Other: steering committee membership ; Janssen: Honoraria, Other; BMS: Honoraria, Other: steering committee membership ; Merk: Honoraria, Other: steering committee membership ; Takeda: Honoraria, Other: steering committee membership ; Amgen: Honoraria, Other: steering committee membership ; Sanofi: Honoraria, Other: steering committee membership steering committee membership ; Novartis: Honoraria, Other: steering committee membership ; Roche: Honoraria; Gilead: Honoraria; Incyte: Honoraria, Other: steering committee membership ; Karyopharm: Honoraria. Decaux:Takeda: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria.
Published: 2018

45. Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial

Author: Olivier Decaux, Philippe Rodon, Philippe Moreau, Laurent Garderet, Claire Mathiot, Jean Marc Virion, Isabelle Azais, Brigitte Pegourie, Chantal Doyen, Pascal Lenain, Thierry Facon, Mamoun Dib, Jean Fontan, Bruno Salles, Jean-Paul Eschard, Cyrille Hulin, Ingrid Lafon, Gaelle Guillerm, Lotfi Benboubker, and Philippe Casassus
Subjects: Male, Melphalan, Cancer Research, medicine.medical_specialty, Maximum Tolerated Dose, medicine.drug_class, Kaplan-Meier Estimate, Neutropenia, Placebo, Risk Assessment, Gastroenterology, Disease-Free Survival, Drug Administration Schedule, Statistics, Nonparametric, chemistry.chemical_compound, Prednisone, Cause of Death, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Geriatric Assessment, Multiple myeloma, Aged, Neoplasm Staging, Probability, Proportional Hazards Models, Aged, 80 and over, Dose-Response Relationship, Drug, business.industry, Age Factors, medicine.disease, Survival Analysis, Nitrogen mustard, Thalidomide, Surgery, Treatment Outcome, Oncology, chemistry, Corticosteroid, Female, Multiple Myeloma, business, Follow-Up Studies, medicine.drug
Abstract: Purpose Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma. Patients and Methods Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival. Results After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003). Conclusion This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.
Published: 2009

46. Phase II study of bendamustine, bortezomib and dexamethasone as second-line treatment for elderly patients with multiple myeloma: the Intergroupe Francophone du Myelome 2009-01 trial

Author: Hervé Avet-Loiseau, Laurent Garderet, Mamoun Dib, Marie-Odile Petillon, Brigitte Kolb, Jean Fontan, Pascal Lenain, Brigitte Pegourie, Murielle Roussel, Jean-Pierre Vilque, Bruno Royer, H. Jardel, Philippe Casassus, Olivier Decaux, Xavier Leleu, Carine Chaleteix, Catherine Traullé, Anne-Marie Stoppa, Pascale Cony-Makhoul, Mourad Tiab, Anne Banos, Riad Benramdane, Philippe Moreau, Philippe Rodon, Cyrille Hulin, Bruno Anglaret, Lotfi Benboubker, Claire Mathiot, Olivier Fitoussi, Thomas Dejoie, Service de Médecine Interne, CH Bretagne Atlantique, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), university hospital, University Hospital, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Géographie-cités (GC (UMR_8504)), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Department of Hematology, Hospices Civils de Lyon (HCL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Laboratoire d'Hématologie biologique, Institut Curie [Paris], Laboratoire de Biochimie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Matériaux Jean Rouxel (IMN), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, CRLCC Henri Becquerel, Géographie-cités ( GC ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Hospices Civils de Lyon ( HCL ), Centre François Baclesse, INSTITUT CURIE, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institut des Matériaux Jean Rouxel ( IMN ), Université de Nantes ( UN ) -Centre National de la Recherche Scientifique ( CNRS ), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Université Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Curie, Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, and Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, Bendamustine, Melphalan, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Phases of clinical research, elderly, Autologous stem-cell transplantation, Prednisone, hemic and lymphatic diseases, Internal medicine, medicine, bendamustine, Online Only Articles, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, relapse, [ SDV ] Life Sciences [q-bio], business.industry, Bortezomib, Hematology, medicine.disease, 3. Good health, Surgery, Thalidomide, multiple myeloma, business, medicine.drug
Abstract: In patients with multiple myeloma (MM) not eligible for high-dose therapy and autologous stem cell transplantation (ASCT), the 2 following options are recommended as part of front-line treatment and approved based on data from randomized phase III trials: melphalan/prednisone/thalidomide (MPT), or
Published: 2015

47. Successful mobilization and engraftment of PBSCs derived from donor cord blood cells after a previous allogeneic RIC single unrelated cord blood transplantation

Author: Jacqueline Chabod, Jean Fontan, Faezeh Legrand, Christophe Ferrand, Jacqueline Vuiller, Philippe Helias, Annie Brion, Caroline Malugani, Eric Deconinck, Marian Heczko, Philippe Delaby, Katell Ledu, Philippe Saas, Fabrice Larosa, Pierre Rohrlich, Fabienne Pouthier, and A. Dormoy
Subjects: Oncology, medicine.medical_specialty, Hematology, Umbilical Cord Blood Transplantation, business.industry, Immunology, Salvage therapy, Cell Biology, Cord Blood Stem Cell Transplantation, Biochemistry, Umbilical cord, Surgery, Transplantation, medicine.anatomical_structure, hemic and lymphatic diseases, Cord blood, Internal medicine, medicine, Stem cell, business
Abstract: To the editor: We describe a successful salvage treatment with intensive chemotherapy and stem cell transplantation for a relapse of Hodgkin lymphoma (HL) after single umbilical cord blood transplantation with a reduced intensity-conditioning regimen (RIC).[1][1],[2][2] The originality of this
Published: 2011

48. IFM2012-03

Author: Xavier Leleu, Guillemette Fouquet, Lionel Karlin, Brigitte Kolb, Mourad Tiab, Carla Araujo, Nathalie Meuleman, Jv Malfuson, Pascal Bourquard, Pascal Lenain, Murielle Roussel, Arnaud Jaccard, Marie-Odile Petillon, Karim Belhadj-Merzoug, Gerard Lepeu, Marie-Lorraine Chretien, Jean Fontan, Philippe Rodon, Anna Schmitt, Fritz Offner, Laurent Voillat, Sophie Cereja, Frederique Kuhnowski, Sophie Rigaudeau, Olivier Decaux, Catherine Humbrecht-Kraut, Jamile Frayfer, Olivier Fitoussi, Damien Roos Weil, Jean Claude Eisenmann, Veronique Dorvaux, Eric G. Voog, Cyrille Hulin, Michel Attal, Philippe Moreau, and Thierry Facon
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Abstract: Background. Melphalan plus prednisone and bortezomib combination is the most frequent standard of care used upfront for newly diagnosed elderly myeloma (eNDMM). Despite significant improvements with bortezomib sub-cutaneous administration and weekly schedule, safety profile issues remain with MPV, that only can be resolved with lowering the doses, albeit of the potential loss of efficacy. Carfilzomib (K), a novel generation proteasome inhibitor, has different safety profile with absence of neuropathy. Carmysap, a phase I/II trial of twice weekly Carfilzomib plus MP in eNDMM, demonstrated carfilzomib MTD at 36mg/m2. The safety profile appeared otherwise good for this frail population. We hypothesized that Carfilzomib can be used on a weekly schedule allowing to increase the dose of Carfilzomib given its positive safety profile. Methods. IFM2012-03 (carmysap weekly) is a phase 1/2 multicenter symptomatic eNDMM (65 and older) study to determine MTD during the phase 1 part and VGPR+CR rate (IMWG criteria) during the phase 2 part of KMP (Carfilzomib Weekly Plus Melphalan and Prednisone) regimen. Inclusion criteria required absolute neutrophils ≥1G/L, untransfused platelet count ≥75G/L, hemoglobine ≥8.5g/dL and clairance creatinine ≥30ml/min. Induction comprised nine 5 weeks cycles. K is given 36, 45, 56 and 70 mg/m2 on days 1, 8, 15, 22 IV route in combination to oral Melphalan 0.25mg/kg/j and oral prednisone 60mg/m2, both on days 1 to 4. Maintenance. Carfilzomib. 36 mg/m2 weekly, every two weeks IV route for 1 year. Melphalan and Prednisone is not pursued at maintenance. Analysis is done on ITT. Recruitment was 6 patients per cohort, 3 DLTs defined MTD at the lower N-1 dose. We will report at ASH the results of the phase 1 and 2. Results. 32 NDMM recruited, 30 treated in the study, 6 per cohort at K 36 mg/m², 45, 56, and 70 twice per DSMB request. The median age was 76 with 2/3rd older than 75, sex ratio M/F 1.2, R-ISS 2 and 3 in 80%.There was one DLT at K 36 (grade 4 lymphopenia), one at 45 (lysis syndrome complicated with grade 4 renal insufficiency, two at 56 (cardiac insufficiency grade 3 and febrile neutropenia grade 3) and 2 at 70 (vomiting grade 3 and liver cholestase enzyme grade 3) across the 2 70 cohorts. As a whole for the study, the ORR is 87.5%, with 45.7% at least in CR. At data cut-off, with a median follow-up at 15 months, one patient had progressed and 2 had died of whom one of cardiac dysfunction considered K related at 56. The safery profile appeared well tolerated, however, 22 SAE were reported for a total of greater than 200 cycles administered of KMP. Of particular interest, 19 SAEs were reported across the K 56 and 70 cohorts, 6 of which were cardiovascular origin. Conclusion. IFM2012-03, KMP weekly, Carfilzomib plus Melphalan and Prednisone in elderly NDMM has reached RP2D at 70mg/m2 of K. The SAE signal at the highest dose of K 70 raise concerns on using K 70 in patients older than 75-80 years old, and the DSMB may recommend for these patients to limit the RP2D at 56mg/m2 of K. Updated data for phase 1 and 2 portions will be presented at ASH for the first time. Disclosures Leleu: TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Karlin:celgene: Consultancy, Honoraria; Bristol: Consultancy; takeda: Consultancy; janssen-cilag: Consultancy, Honoraria; amgen: Consultancy, Honoraria. Meuleman:Celgene: Consultancy; Bristol-Myers-Squibb: Consultancy; Takeda: Consultancy; Amgen: Consultancy. Roussel:AMGEN: Consultancy, Other: lecture fees, Research Funding; sanofi: Other: lecture fees; celgene: Consultancy, Other: lecture fees, Research Funding; janssen: Consultancy, Other: lecture fees; BMS: Other: lecture fees. Decaux:The Binding Site: Other: supply of free light chain assays , Research Funding; SIEMENS: Honoraria, Other: supply of free light chain assays , Research Funding. Hulin:celgene: Honoraria; Bristol: Honoraria; Janssen: Honoraria; Amgen: Honoraria; takeda: Honoraria. Attal:amgen: Consultancy, Research Funding; sanofi: Consultancy; celgene: Consultancy, Research Funding; janssen: Consultancy, Research Funding. Moreau:Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria; Novartis: Honoraria; Bristol-Myers Squibb: Honoraria. Facon:Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Bristol: Consultancy; Janssen: Consultancy, Speakers Bureau; Karyopharm: Consultancy; Novartis: Consultancy; Millenium/Takeda: Consultancy.
Published: 2016

49. Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients

Author: Benjamin Hebraud, Cecile Fohrer, M. Attal, Valérie Lauwers-Cances, François Guilhot, Jill Corre, T. Lamy, Lionel Karlin, Hervé Avet-Loiseau, Laurent Garderet, Murielle Roussel, Catherine Sebban, C Gentil, Thierry Facon, Christophe Fruchart, Denis Caillot, Frédérique Orsini-Piocelle, Mamoun Dib, Jean Fontan, Jérôme Jaubert, Stoppa Am, Brigitte Pegourie, Gérard Lepeu, Philippe Moreau, Xavier Leleu, Claudine Sohn, C. Hulin, Gerald Marit, Sabine Brechignac, and Margaret Macro
Subjects: Oncology, Male, Cancer Research, Prognostic factor, medicine.medical_specialty, Pathology, Multivariate analysis, Article, Cohort Studies, Internal medicine, Medicine, Humans, Multiple myeloma, In Situ Hybridization, Fluorescence, Univariate analysis, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Hematology, medicine.disease, Prognosis, Chromosomes, Human, Pair 1, Homogeneous group, Female, Chromosome Deletion, business, Multiple Myeloma, Cohort study, Fluorescence in situ hybridization
Abstract: Deletions of the 1p region appear as a pejorative prognostic factor in multiple myeloma patients (especially 1p22 and 1p32 deletions) but there is a lack of data on the real impact of 1p abnormalities on an important and homogeneous group of patients. To address this issue we studied by fluorescence in situ hybridization (FISH) the incidence and prognostic impact of 1p22 and 1p32 deletions in 1195 patients from the IFM (Institut Francophone du Myelome) cell collection. Chromosome 1p deletions were present in 23.3% of the patients (271): 15.1% (176) for 1p22 and 7.3% (85) for 1p32 regions. In univariate analyses, 1p22 and 1p32 appeared as negative prognostic factors for progression-free survival (PFS): 1p22: 19.8 months vs 33.6 months (P
Published: 2013

50. Bortezomib, Thalidomide and Dexamethasone (VTD) Is Superior to Bortezomib, Cyclophosphamide and Dexamethasone (VCD) Prior to Autologous Stem Cell Transplantation for Patients with De Novo Multiple Myeloma. Results of the Prospective IFM 2013-04 Trial

Author: Kamel Laribi, Driss Chaoui, Mourad Tiab, Sabine Brechignac, Philippe Moreau, Lucie Planche, Pascal Godmer, Laetitia Biron, Margaret Macro, Cyrille Hulin, Hervé Avet-Loiseau, Karim Belhadj, Murielle Roussel, Marc Wetterwald, Hélène Caillon, Arnaud Jaccard, Gerald Marit, Thomas Dejoie, Brigitte Pegourie, Odile Luycx, Thierry Facon, Denis Caillot, Pascal Lenain, Mamoun Dib, Jean Fontan, Carine Chaleteix, Borhane Slama, Anne-Marie Stoppa, Olivier Allangha, Mathieu Puyade, Véronique Dorvaux, Jean-Paul Fermand, Michel Attal, Martine Escoffre, Carla Araujo, Brigitte Kolb, Bruno Royer, Jean Claude Eisenmann, Laurent Garderet, Sylvie Glaisner, and Philippe Rodon
Subjects: medicine.medical_specialty, business.industry, Immunology, Cell Biology, Hematology, medicine.disease, Biochemistry, law.invention, Thalidomide, Clinical trial, Regimen, Autologous stem-cell transplantation, Randomized controlled trial, law, Internal medicine, medicine, Clinical endpoint, Progression-free survival, business, Multiple myeloma, medicine.drug
Abstract: Background Induction therapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with symptomatic multiple myeloma less than 66 years old. The quality of response to the induction treatment is an important prognostic factor and is predictive of progression free survival (PFS) following ASCT. The triplet combinations bortezomib-thalidomide-dexamethasone (VTD) and bortezomib-cyclophosphamide-dexamethasone (VCD) have demonstrated high response rates in prospective phase 2 and phase 3 clinical trials, they are 2 of the most commonly used induction regimens prior to ASCT, and are both recommended in the International guidelines. To date, no comparative data from prospective randomized trials of the safety and efficacy of VTD vs VCD are available. This provided the rationale for the phase 3 investigation of VTD vs VCD prior to ASCT in patients with de novo MM in this randomized multicenter study (NCT01564537). Methods Patients with de novo symptomatic MM less than 66 years old were prospectively randomized to receive either 4 cycles of VTD (arm A) or 4 cycles of VCD (arm B) followed by ASCT. The VTD regimen consisted of four 21-day cycles of bortezomib 1.3 mg/m²/d, subcutaneously (SC) D1, 4, 8 and 11, Dexamethasone 40 mg/d, PO D1 to 4, D9 to 12 and Thalidomide 100 mg/d, PO D1 to D21. The VCD regimen consisted of four 21-day cycles of bortezomib 1.3 mg/m²/d, SC D1, 4, 8 and 11, Dexamethasone 40 mg/d, PO D1 to 4, D9 to 12 and Cyclophosphamide 500 mg/m²/d, PO D1, 8, 15. Patients were stratified according to ISS (1-2 versus 3) and cytogenetics (high-risk defined by 17p deletion and t(4;14) versus other).The primary endpoint was very good partial response (VGPR) rate following 4 cycles. Response was assessed in a central lab according to the IMWG criteria. Assuming a VGPR rate of 60% in the VTD arm versus 45% in the VCD arm (15% difference), the possibility to detect a statistically significant difference required the enrolment of 340 patients overall (170 per arm). Adverse events were graded using the NCI CTCAE catalogue, version 4.0. Results From 11/2013 to 02/2015, 358 patients were enrolled into the study. 18 were screening failures, and 170 were randomized each to arm A (VTD) and arm B (VCD). The median age was 60 years (range, 26-65), 62% of the patients were male, and overall, the patient characteristics were well-balanced across the 2 arms of the study. The median number of induction cycles administered in both arms was 4 (1-4). On an intent-to-treat basis, the overall response rate (> partial response [PR]) was 92.3% in arm A, including a 10.7% complete response (CR) rate and a VGPR rate of 66.7%, while in arm B the overall response rate was 84%, with a 9.5% CR and a 56.2% VGPR rate. VGPR and PR rates were significantly higher in the VTD arm with p-values of 0.04 and 0.02, respectively. Seven patients died during induction therapy (2%), 3 in arm A from infections (2) and pulmonary embolism (1), and 4 in arm B from progression to extramedullary myeloma (2) and infections (2). Grades 3 / 4 peripheral neuropathy occurred in 4% and 2.2% in Arm A and B, respectively. Grade 3/4 neutropenia was seen in 11.9% vs 22.5% in Arm A and B, respectively. Conclusion This trial is the first prospective randomized comparison of 4 cycles of VTD versus 4 cycles of VCD administered as induction therapy prior to ASCT. VTD was shown to be significantly superior to VCD in terms of VGPR and PR rates. Neuropathy rates low in both arms, while neutropenia was more frequent with VCD. Disclosures Moreau: Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hulin:Celgene Corporation: Honoraria; Janssen: Honoraria; Bristol Myers Squibb: Honoraria; Amgen: Honoraria. MACRO:celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees. Garderet:Bristol-Myers Squibb: Consultancy. Stoppa:Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Laribi:Hospira SAS: Research Funding. Avet-Loiseau:jansen: Membership on an entity's Board of Directors or advisory committees; onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Attal:jansen: Honoraria; celgene: Membership on an entity's Board of Directors or advisory committees.
Published: 2015

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

62 results on '"Jean Fontan"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources