216 results on '"Arnaud Pigneux"'
Search Results
2. Prise en charge des LAM chez les sujets âgés
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Pierre-Yves Dumas and Arnaud Pigneux
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Cancer Research ,Oncology ,Radiology, Nuclear Medicine and imaging ,Hematology ,General Medicine - Published
- 2023
3. First clinical description of a pedigree with complete NAF1 deletion
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Jean Galtier, Sophie Dimicoli-Salazar, Aurélien Trimouille, Elodie Lainey, Patrick Revy, Audrey Bidet, Yoann Vial, Edouard Forcade, Marie-Laure Negrier-Leibreich, Etienne Rivière, Julie Tinat, Nathalie Le Meur, Christelle Ménard, Arnaud Pigneux, Thibaut Leguay, Pierre-Yves Dumas, Ba Ibrahima, and Caroline Kannengiesser
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Cancer Research ,Oncology ,Hematology - Published
- 2022
4. Olutasidenib (FT-2102) Induces Durable Complete Remissions in Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia. Results from a Planned Interim Analysis of a Phase 2 Pivotal Clinical Trial
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Jorge E. Cortes, Pierre Fenaux, Karen Yee, Christian Recher, Andrew H. Wei, Pau Montesinos, David C Taussig, Arnaud Pigneux, Thorsten Braun, Antonio Curti, Carolyn Grove, Brian A. Jonas, Asim Khwaja, Pierre Peterlin, Olga Polyanskaya, Jennifer Sweeney, Julie Brevard, Emma Barrett, and Stephane De Botton
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
5. Prognostic impact of DDX41 germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study
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Nicolas Duployez, Laëtitia Largeaud, Matthieu Duchmann, Rathana Kim, Julie Rieunier, Juliette Lambert, Audrey Bidet, Lise Larcher, Jean Lemoine, François Delhommeau, Pierre Hirsch, Laurène Fenwarth, Olivier Kosmider, Justine Decroocq, Anne Bouvier, Yannick Le Bris, Marlène Ochmann, Alberto Santagostino, Lionel Adès, Pierre Fenaux, Xavier Thomas, Jean-Baptiste Micol, Claude Gardin, Raphael Itzykson, Jean Soulier, Emmanuelle Clappier, Christian Recher, Claude Preudhomme, Arnaud Pigneux, Hervé Dombret, Eric Delabesse, and Marie Sébert
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Male ,Immunology ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,Prognosis ,Biochemistry ,DEAD-box RNA Helicases ,Leukemia, Myeloid, Acute ,Humans ,Female ,Prospective Studies ,Germ-Line Mutation ,Retrospective Studies - Abstract
DDX41 germline mutations (DDX41MutGL) are the most common genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia (AML). Recent reports suggest that DDX41MutGL myeloid malignancies could be considered as a distinct entity, even if their specific presentation and outcome remain to be defined. We describe here the clinical and biological features of 191 patients with DDX41MutGL AML. Baseline characteristics and outcome of 86 of these patients, treated with intensive chemotherapy in 5 prospective Acute Leukemia French Association/French Innovative Leukemia Organization trials, were compared with those of 1604 patients with DDX41 wild-type (DDX41WT) AML, representing a prevalence of 5%. Patients with DDX41MutGL AML were mostly male (75%), in their seventh decade, and with low leukocyte count (median, 2 × 109/L), low bone marrow blast infiltration (median, 33%), normal cytogenetics (75%), and few additional somatic mutations (median, 2). A second somatic DDX41 mutation (DDX41MutSom) was found in 82% of patients, and clonal architecture inference suggested that it could be the main driver for AML progression. DDX41MutGL patients displayed higher complete remission rates (94% vs 69%; P < .0001) and longer restricted mean overall survival censored at hematopoietic stem cell transplantation (HSCT) than 2017 European LeukemiaNet intermediate/adverse (Int/Adv) DDX41WT patients (5-year difference in restricted mean survival times, 13.6 months; P < .001). Relapse rates censored at HSCT were lower at 1 year in DDX41MutGL patients (15% vs 44%) but later increased to be similar to Int/Adv DDX41WT patients at 3 years (82% vs 75%). HSCT in first complete remission was associated with prolonged relapse-free survival (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88; P = .02) but not with longer overall survival (hazard ratio, 0.77; 95% confidence interval, 0.35-1.68; P = .5).
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- 2022
6. Dexaml-02 : A Phase II Study of Dexamethasone Added to Induction and Postremission Therapy in Older Patients with Newly Diagnosed AML. a French Innovative Leukemia Organization (FILO) Study
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Christian Recher, Sarah Bertoli, Pierre Peterlin, Romain Guieze, Yohan Desbrosses, Yosr Hicheri, Omar Benbrahim, Martin Carre, Hunault-Berger Mathilde, Anne Banos, Marc Bernard, Emmanuel Gyan, Alain Saad, Safia Chebrek, Gabrielle Roth Guepin, Veronique Dorvaux, Laurence Sanhes, Maria Pilar Gallego Hernanz, Carole Exbrayat, Laure Vincent, Chantal Himberlin, Laetitia Largeaud, Eric Delabesse, Francois Vergez, Norbert Vey, Ariane C Mineur, Célestine Simand, Isabelle Luquet, and Arnaud Pigneux
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
7. Initial Results from SELECT-AML-1, a Phase 2 Study of Tamibarotene in Combination with Venetoclax and Azacitidine in RARA-Positive Newly Diagnosed AML Patients Ineligible for Standard Induction Chemotherapy
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Suman Kambhampati, Christine M. McMahon, Alireza Eghtedar, Daniel A. Pollyea, Stephane de Botton, Arnaud Pigneux, Mohamad Cherry, Brian J Ball, Gautam Borthakur, Thomas Cluzeau, Gary J. Schiller, Beibei Hu, Angela Volkert, Joanie Aasen Gausman, Graeme Hodgson, David A. Roth, Erica D. Warlick, Michael J. Kelly, and Eytan Stein
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
8. Epag 2015 : A Phase II Randomized Placebo-Controlled Study to Assess the Impact on Outcome of Eltrombopag Administered to Elderly Patients with Acute Myeloid Leukemia Receiving Induction Chemotherapy. a French Innovative Leukemia Organization (FILO) Study
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Arnaud Pigneux, Pierre-Yves Dumas, Marc Bernard, Norbert Vey, Audrey Bidet, Ariane Mineur, Mathilde Hunault, Martin Carre, Mario Ojeda, Anne Banos, Pierre Peterlin, Romain Guieze, Yohan Desbrosses, Gabrielle Roth Guepin, Celestine Simand, Thibaut Leguay, Emmanuel Gyan, Eric Jourdan, Jean-Philippe Vial, Tony Marchand, Yosr Hicheri, Marie C Bene, Jean Francois Hamel, and Christian Recher
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
9. UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
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Nicolas Duployez, Loïc Vasseur, Rathana Kim, Laëtitia Largeaud, Marie Passet, Anaïs L’Haridon, Pierre Lemaire, Laurène Fenwarth, Sandrine Geffroy, Nathalie Helevaut, Karine Celli‑Lebras, Lionel Adès, Delphine Lebon, Céline Berthon, Alice Marceau-Renaut, Meyling Cheok, Juliette Lambert, Christian Récher, Emmanuel Raffoux, Jean-Baptiste Micol, Arnaud Pigneux, Claude Gardin, Eric Delabesse, Jean Soulier, Mathilde Hunault, Hervé Dombret, Raphael Itzykson, Emmanuelle Clappier, Claude Preudhomme, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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), Université de Toulouse (UT), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), 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), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Thérapie génique et contrôle de l'expansion cellulaire (UMR E007), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'hématologie adulte [Hôpital de Saint Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Hôpital Haut-Lévêque, and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
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Cancer Research ,Oncology ,Hematology ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3-ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence of FLT3-ITD. UBTF-TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) than UBTF-wild-type patients. In patients enrolled in the ALFA-0702 study (n = 614 patients including 21 with UBTF-TD AML), the 3-year disease-free survival (DFS) and overall survival of UBTF-TD patients were 42.9% (95%CI: 23.4–78.5%) and 57.1% (95%CI: 39.5–82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests that WT1-mutated clones are frequently selected under ICT. This study supports the recognition of UBTF-TD AML as a new AML entity in adults.
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- 2023
10. Impact of Mutational Status and Prognostic Factors on Survival in Chronic Myelomonocytic Leukemia With Systemic Inflammation and Autoimmune Disorders
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Charles Dussiau, Henry Dupuy, Audrey Bidet, Mathieu Sauvezie, Anne-Charlotte De-Grande, Lisa Boureau, Etienne Riviere, Edouard Forcade, Fabrice Bonnet, Pierre-Yves Dumas, Pierre Duffau, Arnaud Pigneux, Jean-François Viallard, Sophie Dimicoli-Salazar, Estibaliz Lazaro, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Global Health in the Global South (GHiGS), Institut de Recherche pour le Développement (IRD)- Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Hematology - Published
- 2023
11. Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML
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Stéphane de Botton, Pierre Fenaux, Karen W.L. Yee, Christian Récher, Andrew H Wei, Pau Montesinos, David C. Taussig, Arnaud Pigneux, Thorsten Braun, Antonio Curti, Carolyn S Grove, Brian A. Jonas, Asim Khwaja, Ollivier Legrand, Pierre Peterlin, Montserrat Arnan, William Blum, Daniela Cilloni, Devendra K. Hiwase, Joseph G. Jurcic, Jürgen Krauter, Xavier Thomas, Justin M Watts, Jay Yang, Olga Polyanskaya, Julie Brevard, Jennifer Sweeney, Emma Barrett, and Jorge Cortes
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Hematology - Abstract
Olutasidenib (FT-2102) is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1). Overall, 153 IDH-1 inhibitor naïve patients with mIDH1R132 relapsed/refractory (R/R) acute myeloid leukemia (AML) received olutasidenib monotherapy 150 mg twice daily in the pivotal cohort of this study. Median age (range) was 71 years (32-87) and the median number of prior regimens was 2 (1-7). The rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh) was 35% (n=51; 95% CI, 27.0-43.0) and the overall response rate was 48% (n=71; 95% CI, 40.0-56.7). Response rates were similar in patients who had and who had not received prior venetoclax. With 55% of patients censored at the time of data cut-off, median duration of CR/CRh was 25.9 months (95% CI, 13.5-NE). Median duration of overall response was 11.7 months (95% CI, 6.9-25.9). Median overall survival was 11.6 months (95% CI, 8.9-15.5). Of 86 patients who were transfusion-dependent at baseline, a 56-day transfusion independence was achieved in 29 (34%), including patients in all response groups. Grade 3/4 treatment-emergent adverse events (≥10%) were febrile neutropenia and anemia (n=31; 20% each), thrombocytopenia (n=25; 16%), and neutropenia (n=20; 13%). Differentiation syndrome adverse events of special interest occurred in 22 (14%) patients, with 14 (9%) grade ≥3 and 1 fatal case reported. Overall, olutasidenib induced durable remissions and transfusion independence with a well-characterized and manageable side-effect profile. The observed efficacy represents a therapeutic advance in this molecularly defined, poor-prognosis patient population with mIDH1 R/R AML. This trial is registered at www.clinicaltrials.gov as NCT02719574.
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- 2023
12. Azacitidine, intensive chemotherapy or best supportive care in relapsed or refractory acute myeloid leukemia, a DATAML registry study
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Noémie Gadaud, Harmony Leroy, Emilie Bérard, Suzanne Tavitian, Thibaut Leguay, Sophie Dimicoli-Salazar, Jean-Baptiste Rieu, Isabelle Luquet, Laetitia Largeaud, Audrey Bidet, Eric Delabesse, Emilie Klein, Audrey Sarry, Anne-Charlotte de Grande, Pierre Bories, Arnaud Pigneux, Christian Récher, Pierre-Yves Dumas, and Sarah Bertoli
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Antimetabolites, Antineoplastic ,Leukemia, Myeloid, Acute ,Cancer Research ,Treatment Outcome ,Oncology ,Chronic Disease ,Azacitidine ,Humans ,Registries ,Hematology - Abstract
We analyzed 526 consecutive acute myeloid leukemia patients refractory to or relapsing after chemotherapy. 270 patients received intensive salvage chemotherapy (IC), 97 azacitidine (AZA) and 159 best supportive care (BSC). Complete response was obtained in 37/19/0% (
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- 2022
13. Early detection of WT1 measurable residual disease identifies high-risk patients, independent of transplantation in AML
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Hervé Dombret, Karine Celli-Lebras, Arnaud Pigneux, Sylvie Castaigne, Aline Renneville, Christine Terré, Alice Marceau-Renaut, Nicolas Boissel, Jean-Baptiste Micol, Sandrine Hayette, Claude Preudhomme, Céline Berthon, Philippe Rousselot, Jérôme Lambert, Juliette Lambert, Emmanuelle Clappier, Christian Recher, Nicolas Duployez, Xavier Thomas, Emmanuel Raffoux, Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), and HAL UVSQ, Équipe
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Adult ,Oncology ,medicine.medical_specialty ,Neoplasm, Residual ,Adolescent ,[SDV]Life Sciences [q-bio] ,Population ,Early detection ,Disease ,Young Adult ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,WT1 Proteins ,education ,education.field_of_study ,High risk patients ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Induction chemotherapy ,Hematology ,Middle Aged ,Prognosis ,[SDV] Life Sciences [q-bio] ,body regions ,Transplantation ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Bone marrow ,business - Abstract
WT1 overexpression is frequently identified in acute myeloid leukemia (AML) and has been reported to be a potential marker for monitoring measurable residual disease (MRD). We evaluated the use of postinduction WT1 MRD level as a prognostic factor, as well as the interaction between postinduction WT1 MRD response and the effect of allogeneic stem cell transplantation (allo-SCT) in the first complete remission (CR). In the ALFA-0702 trial, patients with AML, aged 18 to 59, had a prospective quantification of WT1 MRD. The occurrence of a WT1 MRD ratio >2.5% in bone marrow or >0.5% in peripheral blood was defined as MRDhigh, and ratios below these thresholds were defined as MRDlow. The prognostic value of MRD after induction chemotherapy was assessed in 314 patients in first CR by comparing the risk of relapse, the relapse-free survival (RFS), and the overall survival (OS). Interaction between MRD response and the allo-SCT effect was evaluated in patients by comparing the influence of allo-SCT on the outcomes of patients with MRDhigh with those with MRDlow. The results showed that patients with MRDhigh after induction had a higher risk of relapse and a shorter RFS and OS. The MRD response remained of strong prognostic value in the subset of 225 patients with intermediate-/unfavorable-risk AML who were eligible for allo-SCT, because patients with MRDhigh had a significantly higher risk of relapse resulting in worse RFS and OS. The effect of allo-SCT was higher in patients with MRDlow than in those with MRDhigh, but not significantly different. The early WT1 MRD response highlights a population of high-risk patients in need of additional therapy.
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- 2021
14. Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial
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Stéphane de Botton, Pau Montesinos, Andre C. Schuh, Cristina Papayannidis, Paresh Vyas, Andrew H. Wei, Hans Ommen, Sergey Semochkin, Hee-Je Kim, Richard A. Larson, Jaime Koprivnikar, Olga Frankfurt, Felicitas Thol, Jörg Chromik, Jenny Byrne, Arnaud Pigneux, Xavier Thomas, Olga Salamero, Maria Belen Vidriales, Vadim Doronin, Hartmut Döhner, Amir T. Fathi, Eric Laille, Xin Yu, Maroof Hasan, Patricia Martin-Regueira, Courtney D. DiNardo, Institut Català de la Salut, [de Botton S] Gustave Roussy, Université Paris-Saclay, Villejeuf, France. [Montesinos P] Hospital Universitari i Politecnic La Fe, Valencia, Spain. [Schuh AC] Princess Margaret Cancer Centre, Toronto, ON, Canada. [Papayannidis C] IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', Bologna, Italy. [Vyas P] Oxford Biomedical Research Centre and Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom. [Wei AH] The Alfred Hospital, Melbourne, VIC, Australia. Monash University, Melbourne, VIC, Australia. [Salamero O] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Otros calificadores::/uso terapéutico [Otros calificadores] ,Immunology ,Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES] ,Medicaments antineoplàstics - Ús terapèutic ,Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute [DISEASES] ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] ,Cell Biology ,Hematology ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Biochemistry ,neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda [ENFERMEDADES] ,Anomalies cromosòmiques ,Leucèmia mieloide aguda - Aspectes genètics ,Leucèmia mieloide aguda - Tractament ,Other subheadings::/therapeutic use [Other subheadings] ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] ,fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS] - Abstract
Enasidenib; Conventional care Enasidenib; Atenció convencional Enasidenib; Atención convencional This open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 (isocitrate dehydrogenase 2) inhibitor, with conventional care regimens (CCRs) in patients aged ≥60 years with late-stage, mutant-IDH2 acute myeloid leukemia (AML) relapsed/refractory (R/R) to 2 or 3 prior AML-directed therapies. Patients were first preselected to a CCR (azacitidine, intermediate-dose cytarabine, low-dose cytarabine, or supportive care) and then randomized (1:1) to enasidenib 100 mg per day or CCR. The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS), time to treatment failure (TTF), overall response rate (ORR), hematologic improvement (HI), and transfusion independence (TI). Overall, 319 patients were randomized to enasidenib (n = 158) or CCR (n = 161). The median age was 71 years, median (range) enasidenib exposure was 142 days (3 to 1270), and CCR was 36 days (1 to 1166). One enasidenib (0.6%) and 20 CCR (12%) patients received no randomized treatment, and 30% and 43%, respectively, received subsequent AML-directed therapies during follow-up. The median OS with enasidenib vs CCR was 6.5 vs 6.2 months (HR [hazard ratio], 0.86; P = .23); 1-year survival was 37.5% vs 26.1%. Enasidenib meaningfully improved EFS (median, 4.9 vs 2.6 months with CCR; HR, 0.68; P = .008), TTF (median, 4.9 vs 1.9 months; HR, 0.53; P < .001), ORR (40.5% vs 9.9%; P
- Published
- 2022
15. Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO
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Pierre-Yves Dumas, Emmanuel Raffoux, Emilie Bérard, Sarah Bertoli, Marie-Anne Hospital, Maël Heiblig, Yohann Desbrosses, Caroline Bonmati, Cécile Pautas, Juliette Lambert, Corentin Orvain, Anne Banos, Florence Pasquier, Pierre Peterlin, Tony Marchand, Madalina Uzunov, Jamilé Frayfer, Pascal Turlure, Thomas Cluzeau, Eric Jourdan, Chantal Himberlin, Emmanuelle Tavernier, Alban Villate, Stephanie Haiat, Marie-Lorraine Chretien, Martin Carre, Sylvain Chantepie, Ioana Vaida, Mathieu Wemeau, Safia Chebrek, Gaelle Guillerm, Romain Guièze, Houria Debarri, Eve Gehlkopf, Kamel Laribi, Ambroise Marcais, Alberto Santagostino, Marie-Christine Béné, Ariane Mineur, Arnaud Pigneux, Hervé Dombret, and Christian Récher
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Cancer Research ,Oncology ,Hematology - Abstract
The real-world efficacy and safety of gilteritinib was assessed in an ambispective study that included 167 R/R FLT3-mutated AML patients. Among them, 140 received gilteritinib as single agent (cohort B), including 67 previously treated by intensive chemotherapy and midostaurin (cohort C). The main differences in patient characteristics in this study compared to the ADMIRAL trial were ECOG ≥ 2 (83.6% vs. 16.6%), FLT3-TKD mutation (21.0% vs. 8.5%), primary induction failure (15.0% vs. 40.0%) and line of treatment (beyond 2nd in 37.1% vs. 0.0%). The rates of composite complete remission, excluding those that occurred after hematopoietic stem cell transplantation (HSCT), were similar at respectively 25.4% and 27.5% in cohorts B and C. Median overall survival (OS) for these two groups was also similar at respectively 6.4 and 7.8 months. Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.
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- 2022
16. A scoring system for AML patients aged 70 years or older, eligible for intensive chemotherapy: a study based on a large European data set using the DATAML, SAL, and PETHEMA registries
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Emilie Bérard, Christoph Röllig, Sarah Bertoli, Arnaud Pigneux, Suzanne Tavitian, Michael Kramer, Hubert Serve, Martin Bornhäuser, Uwe Platzbecker, Carsten Müller-Tidow, Claudia D. Baldus, David Martínez-Cuadrón, Josefina Serrano, Pilar Martínez-Sánchez, Eduardo Rodríguez Arbolí, Cristina Gil, Juan Bergua, Teresa Bernal, Adolfo de la Fuente Burguera, Eric Delabesse, Audrey Bidet, Pierre-Yves Dumas, Pau Montesinos, and Christian Récher
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Leukemia, Myeloid, Acute ,Oncology ,Mutation ,Humans ,Nuclear Proteins ,Hematology ,Registries ,Neoplasm Recurrence, Local ,Prognosis ,Nucleophosmin ,Aged - Abstract
In a context of therapeutic revolution in older adults with AML, it is becoming increasingly important to select patients for the various treatment options by taking account of short-term efficacy and toxicity as well as long-term survival. Here, the data from three European registries for 1,199 AML patients aged 70 years or older treated with intensive chemotherapy were used to develop a prognostic scoring system. The median follow-up was 50.8 months. In the training set of 636 patients, age, performance status, secondary AML, leukocytosis, and cytogenetics, as well as NPM1 mutations (without FLT3-ITD), were all significantly associated with overall survival, albeit not to the same degree. These factors were used to develop a score that predicts long-term overall survival. Three risk-groups were identified: a lower, intermediate and higher-risk score with predicted 5-year overall survival (OS) probabilities of ≥12% (n = 283, 51%; median OS = 18 months), 3–12% (n = 226, 41%; median OS = 9 months) and n = 47, 8%; median OS = 3 months), respectively. This scoring system was also significantly associated with complete remission, early death and relapse-free survival; performed similarly in the external validation cohort (n = 563) and showed a lower false-positive rate than previously published scores. The European Scoring System ≥70, easy for routine calculation, predicts long-term survival in older AML patients considered for intensive chemotherapy.
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- 2022
17. Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: phase 1 results of a phase 1/2 trial
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Justin M, Watts, Maria R, Baer, Jay, Yang, Thomas, Prebet, Sangmin, Lee, Gary J, Schiller, Shira N, Dinner, Arnaud, Pigneux, Pau, Montesinos, Eunice S, Wang, Karen P, Seiter, Andrew H, Wei, Stephane, De Botton, Montserrat, Arnan, Will, Donnellan, Anthony P, Schwarer, Christian, Récher, Brian A, Jonas, P Brent, Ferrell, Christophe, Marzac, Patrick, Kelly, Jennifer, Sweeney, Sanjeev, Forsyth, Sylvie M, Guichard, Julie, Brevard, Patrick, Henrick, Hesham, Mohamed, and Jorge E, Cortes
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Hematology - Abstract
Olutasidenib (FT-2102) is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aims for phase 1 of this phase 1/2 study were to assess the safety, pharmacokinetics, pharmacodynamics, and clinical activity of olutasidenib, as monotherapy or in combination with azacitidine, in patients with acute myeloid leukaemia or myelodysplastic syndrome, harbouring mutant IDH1.In this phase 1/2, multicentre, open-label clinical trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia or intermediate, high, or very high risk myelodysplastic syndrome harbouring mutant IDH1 at 18 study sites in the USA, Australia, France, and Spain. Other key eligibility criteria included Eastern Cooperative Oncology Group performance status 0-2 with adequate liver and renal function. The primary outcomes were dose-limiting toxicities and the maximum tolerated dose, maximum evaluated dose, and the recommended phase 2 dose of olutasidenib. Olutasidenib was administered orally in doses of 150 mg once daily, 150 mg twice per day, and 300 mg once daily. Azacitidine (75 mg/mPatients were enrolled between Aug 8, 2016, and Nov 14, 2018. 78 patients received olutasidenib as monotherapy (n=32) or in combination with azacitidine (n=46). The median follow-up was 8·3 months (IQR 3·1-13·3) for monotherapy and 10·1 months (4·2-15·3) for combination therapy. 16 (50%) of 32 patients in the monotherapy group and 24 (52%) of 46 patients in the combination therapy group were women. Most patients were White (26 [81%] for monotherapy and 31 [67%] for combination therapy). No dose-limiting toxicities were reported in the dose-escalation cohorts and 150 mg twice per day was declared the recommended phase 2 dose on the basis of safety, pharmacokinetics and pharmacodynamics, and clinical activity. The most common (≥20%) grade 3-4 treatment-emergent adverse events with monotherapy were thrombocytopenia (nine [28%] of 32 patients), febrile neutropenia (seven [22%] of 32), and anaemia (seven [22%] of 32); and with combination therapy were thrombocytopenia (19 [41%] of 46), febrile neutropenia (13 [28%] of 46), neutropenia (13 [28%] of 46), and anaemia (nine [20%] of 46). 11 (34%) of 32 patients in the monotherapy group and nine (20%) of 46 patients in the combination therapy group died (most commonly from disease progression [three (9%) of 32 and four (9%) of 46]). No deaths were considered study-drug related. For patients with relapsed or refractory acute myeloid leukaemia, 41% (95% CI 21-64; nine of 22) receiving monotherapy and 46% (27-67; 12 of 26) receiving combination therapy had an overall response. For treatment-naive patients with acute myeloid leukaemia, 25% (1-81; one of four) receiving monotherapy and 77% (46-95; ten of 13) receiving combination therapy had an overall response.Olutasidenib, with or without azacitidine, was well tolerated and showed meaningful clinical activity in patients with IDH1-mutated acute myeloid leukaemia. The results of this phase 1 study provide rationale for the continued evaluation of olutasidenib in multiple patient populations with myeloid malignancies.Forma Therapeutics.
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- 2022
18. Outcomes of patients with IDH1-mutant relapsed or refractory acute myeloid leukemia receiving ivosidenib who proceeded to hematopoietic stem cell transplant
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Stephanie M. Kapsalis, Arnaud Pigneux, Harry P. Erba, Sung Choe, Courtney D. DiNardo, Gail J. Roboz, Hua Liu, Eytan M. Stein, Justin M. Watts, Robert H. Collins, Stéphane de Botton, Bin Wu, Hongfang Wang, Geoffrey L. Uy, Jessica K. Altman, and Thomas Winkler
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Adult ,Male ,Cancer Research ,IDH1 ,Pyridines ,Mutant ,Glycine ,Antineoplastic Agents ,Article ,Text mining ,Refractory ,Humans ,Medicine ,Aged ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematopoietic stem cell ,Myeloid leukemia ,Hematology ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Isocitrate Dehydrogenase ,Survival Rate ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Oncology ,Drug Resistance, Neoplasm ,Mutation ,Cancer research ,Female ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Published
- 2021
19. Looking for somatic mutations in UBA1 in patients with chronic myelomonocytic leukemia associated with systemic inflammation and autoimmune diseases
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Joël Decombe, Audrey Bidet, Anne-Charlotte De-Grande, Pierre-Yves Dumas, Estibaliz Lazaro, Pierre Duffau, Jean-François Viallard, Charles Dussiau, Etienne Rivière, Mathieu Sauvezie, Henry Dupuy, Arnaud Pigneux, Sophie Dimicoli-Salazar, Edouard Forcade, Fabrice Bonnet, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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0303 health sciences ,Cancer Research ,Somatic cell ,business.industry ,Chronic myelomonocytic leukemia ,Hematology ,UBA1 ,Systemic inflammation ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,medicine ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,In patient ,medicine.symptom ,business ,030304 developmental biology - Published
- 2021
20. Antifungal Stewardship in Hematology: Reflection of a Multidisciplinary Group of Experts
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Mauricette Michallet, Jean-Pierre Gangneux, Gilbert Deray, Jean-Paul Mira, Raoul Herbrecht, Jean-François Timsit, Arnaud Pigneux, Yasmine Nivoix, Serge Alfandari, Patricia Ribaud, Mohamad Sobh, Ibrahim Yakoub-Agha, and Dominique Larrey
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0301 basic medicine ,Antifungal ,Cancer Research ,medicine.medical_specialty ,Antifungal Agents ,Hematology ,business.industry ,medicine.drug_class ,030106 microbiology ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Multidisciplinary approach ,Internal medicine ,medicine ,Humans ,Medical physics ,Prospective Studies ,030212 general & internal medicine ,Stewardship ,business - Abstract
We have presented a practical guide developed by a working group of experts in infectious diseases and hematology to summarize the different recommendations issued by the different international groups on antifungal agents used for hematology patients. In addition, a working group of experts in the domains of nephrology, hepatology, and drug interactions have reported their different recommendations when administering antifungal agents, including dose adjustments, monitoring, and management of their side effects. This guide will enable prescribers to have a document available that will allow for better and optimal use of antifungal agents for hematology patients with consideration of the toxicity and interactions adjusted to each indication.
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- 2021
21. VANDA regimen followed by blinatumomab leads to favourable outcome in patients with Philadelphia chromosome-negative B-precursor acute lymphoblastic leukaemia in first relapse
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Luc Heraudet, Jean Galtier, Simon Favre, Florent Peyraud, Titouan Cazaubiel, Harmony Leroy, Nathan Mottal, François‐Xavier Gros, Edouard Forcade, Laurence Clément, Pierre‐Yves Dumas, Arnaud Pigneux, and Thibaut Leguay
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Adult ,Recurrence ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Acute Disease ,Antibodies, Bispecific ,Humans ,Antineoplastic Agents ,Philadelphia Chromosome ,Hematology ,Neoplasm Recurrence, Local ,Precursor Cell Lymphoblastic Leukemia-Lymphoma - Abstract
Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia (R/R BCP-ALL) have very poor outcome. Blinatumomab as single agent has shown activity in R/R BCP-ALL. We aimed to assess the activity of blinatumomab in concomitant association with intensive chemotherapy. Seventeen patients with R/R BCP-ALL were treated with combination of blinatumomab and VANDA (etoposide, cytarabine, mitoxantrone, dexamethasone and asparaginase) regimen. Complete remission (CR) was achieved in 14/17 patient (82%) and 11/17 (65%) were transplanted. One-year leukaemia-free survival was 58.8% for the whole cohort and 90.9% for transplanted patients. These preliminary data suggest that the VANDA-blinatumomab salvage regimen leads to a very high rate of CR and HSCT in suitable patients.
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- 2022
22. Phenotypically-defined stages of leukemia arrest predict main driver mutations subgroups, and outcome in acute myeloid leukemia
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François Vergez, Laetitia Largeaud, Sarah Bertoli, Marie-Laure Nicolau, Jean-Baptiste Rieu, Inès Vergnolle, Estelle Saland, Audrey Sarry, Suzanne Tavitian, Françoise Huguet, Muriel Picard, Jean-Philippe Vial, Nicolas Lechevalier, Audrey Bidet, Pierre-Yves Dumas, Arnaud Pigneux, Isabelle Luquet, Véronique Mansat-De Mas, Eric Delabesse, Martin Carroll, Gwenn Danet-Desnoyers, Jean-Emmanuel Sarry, and Christian Récher
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Leukemia, Myeloid, Acute ,Oncology ,Core Binding Factor Alpha 2 Subunit ,Mutation ,Humans ,Hematology ,HLA-DR Antigens ,Immunophenotyping - Abstract
Classifications of acute myeloid leukemia (AML) patients rely on morphologic, cytogenetic, and molecular features. Here we have established a novel flow cytometry-based immunophenotypic stratification showing that AML blasts are blocked at specific stages of differentiation where features of normal myelopoiesis are preserved. Six stages of leukemia differentiation-arrest categories based on CD34, CD117, CD13, CD33, MPO, and HLA-DR expression were identified in two independent cohorts of 2087 and 1209 AML patients. Hematopoietic stem cell/multipotent progenitor-like AMLs display low proliferation rate, inv(3) or RUNX1 mutations, and high leukemic stem cell frequency as well as poor outcome, whereas granulocyte–monocyte progenitor-like AMLs have CEBPA mutations, RUNX1-RUNX1T1 or CBFB-MYH11 translocations, lower leukemic stem cell frequency, higher chemosensitivity, and better outcome. NPM1 mutations correlate with most mature stages of leukemia arrest together with TET2 or IDH mutations in granulocyte progenitors-like AML or with DNMT3A mutations in monocyte progenitors-like AML. Overall, we demonstrate that AML is arrested at specific stages of myeloid differentiation (SLA classification) that significantly correlate with AML genetic lesions, clinical presentation, stem cell properties, chemosensitivity, response to therapy, and outcome.
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- 2022
23. Delivering HDAC over 3 or 5 days as consolidation in AML impacts health care resource consumption but not outcome
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Isabelle Luquet, Emilie Klein, Jean Galtier, François Vergez, Arnaud Pigneux, Audrey Bidet, Pierre-Yves Dumas, Anne-Charlotte de Grande, Audrey Sarry, Héloïse Rey, Fabien Despas, Jean Baptiste Rieu, Suzanne Tavitian, Nicolas Lechevalier, Emilie Bérard, Thibaut Leguay, Christian Recher, Camille Alric, Jean-Philippe Vial, Sarah Bertoli, and Eric Delabesse
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Adult ,medicine.medical_specialty ,Myeloid ,Disease-Free Survival ,Interquartile range ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cumulative incidence ,Retrospective Studies ,Myeloid Neoplasia ,business.industry ,Retrospective cohort study ,Hematology ,Middle Aged ,medicine.disease ,Minimal residual disease ,Leukemia, Myeloid, Acute ,Leukemia ,Regimen ,medicine.anatomical_structure ,Cytarabine ,business ,Delivery of Health Care ,medicine.drug - Abstract
Postremission treatment is crucial to prevent relapse in acute myeloid leukemia (AML). High-dose cytarabine delivered every 12 hours on days 1, 3, and 5 (HDAC-135) is the standard of care for younger adult patients with AML. Although this standard has been unsuccessfully challenged by other treatment regimens, including multiagent chemotherapy, the timing of HDAC administration has attracted little attention. Here, we retrospectively compared the safety, efficacy, and health care resource consumption associated with HDAC-135 and another standard, condensed HDAC-123 regimen, as consolidation treatment in younger AML patients in first complete response. This study included 221 patients (median age, 46.6 years; range, 18-60 years). HDAC-123 and HDAC-135 were used in 92 and 129 patients, respectively. Both regimens were associated with similar rates of relapse-free survival, cumulative incidence of relapse, nonrelapse mortality, and overall survival, including in core binding factor AML subgroup in which levels of minimal residual disease reduction were similar in both schedules. Hematological recovery times regarding neutrophils and platelets were significantly shorter in patients receiving HDAC-123, with an average difference of 3 to 4 days for each consolidation cycle. The total duration of hospitalization for the whole postremission program was shorter with HDAC-123 (32 days; interquartile ratio [IQR], 22.0,36.5) compared with HDAC-135 (41 days; IQR, 30.5, 50.0) (P < .0001). In conclusion, the condensed HDAC-123 regimen induced faster hematological recovery and therefore significantly reduced the length of hospital stay without affecting treatment response or outcome in younger AML patients.
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- 2020
24. Long-term survival after intensive chemotherapy or hypomethylating agents in AML patients aged 70 years and older: a large patient data set study from European registries
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Audrey Bidet, Hubert Serve, Pierre-Yves Dumas, Carsten Müller-Tidow, Josefina Serrano, Teresa Bernal, Sarah Bertoli, Juan Bergua, Eduardo Rodriguez Arbolí, Uwe Platzbecker, Pilar Martínez-Sánchez, Martin Bornhäuser, Eric Delabesse, Adolfo de la Fuente Burguera, Christian Recher, Arnaud Pigneux, Michael Kramer, Claudia D. Baldus, David Martínez-Cuadrón, Pau Montesinos, Emilie Bérard, Cristina Gil, Christoph Röllig, and Suzanne Tavitian
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Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,EARLY DEATH ,NEWLY-DIAGNOSED AML ,Intensive chemotherapy ,ACUTE MYELOID-LEUKEMIA ,REGIMENS ,Lower risk ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Long term survival ,MANAGEMENT ,Humans ,Medicine ,In patient ,VENETOCLAX ,Registries ,ELDERLY-PATIENTS ,AZACITIDINE ,Aged ,Aged, 80 and over ,Chemotherapy ,EPIGENETIC THERAPY ,business.industry ,Significant difference ,Myeloid leukemia ,Hematology ,Patient data ,CARE ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Oncology ,Azacitidine ,business - Abstract
The outcome of acute myeloid leukemia patients aged 70 years or older is poor. Defining the best treatment option remains controversial especially when choosing between intensive chemotherapy and hypomethylating agents. We set up a multicentric European database collecting data of 3 700 newly diagnosed acute myeloid leukemia patients ≥70 years. The primary objective was to compare overall survival in patients selected for intensive chemotherapy (n = 1199) or hypomethylating agents (n = 1073). With a median follow-up of 49.5 months, the median overall survival was 10.9 (95% CI: 9.7–11.6) and 9.2 months (95% CI: 8.3–10.2) with chemotherapy and hypomethylating agents, respectively. Complete remission or complete remission with incomplete hematologic recovery was 56.1% and 19.7% with chemotherapy and hypomethylating agents, respectively (P
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- 2022
25. Overlapping features of therapy-related and de novoNPM1-mutated AML
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Jad Othman, Manja Meggendorfer, Enrico Tiacci, Christian Thiede, Richard Schlenk, Richard Dillon, Sebastian Stasik, Alessandra Venanzi, Sarah Bertoli, Eric Delabesse, Pierre-Yves Dumas, Arnaud Pigneux, Audrey Bidet, Amanda F. Gilkes, Ian Thomas, Maria Teresa Voso, Alessandro Rambaldi, Lorenzo Brunetti, Vincenzo M. Perriello, Vibeke Andresen, Bjorn T. Gjertsen, Maria Paola Martelli, Christian Récher, Christoph Röllig, Martin Bornhäuser, Hubert Serve, Carsten Müller-Tidow, Claudia D. Baldus, Tortsten Haferlach, Nigel Russell, and Brunangelo Falini
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Immunology ,Cell Biology ,Hematology ,Settore MED/15 ,Biochemistry - Abstract
NPM 1-mutated acute myeloid leukemia (AML) shows unique features. However, the characteristics of “therapy-related” NPM1-mutated AML (t-NPM1 AML) are poorly understood. We compared the genetics, transcriptional profile, and clinical outcomes of t-NPM1 AML, de novo NPM1-mutated AML (dn-NPM1 AML), and therapy-related AML (t-AML) with wild-type NPM1 (t-AML). Normal karyotype was more frequent in t-NPM1 AML (n = 78/96, 88%) and dn-NPM1 (n = 1986/2394, 88%) than in t-AML (n = 103/390, 28%; P < .001). DNMT3A and TET2 were mutated in 43% and 40% of t-NPM1 AML (n = 107), similar to dn-NPM1 (n = 88, 48% and 30%; P > 0.1), but more frequently than t-AML (n = 162; 14% and 10%; P < 0.001). Often mutated in t-AML, TP53 and PPM1D were wild-type in 97% and 96% of t-NPM1 AML, respectively. t-NPM1 and dn-NPM1 AML were transcriptionally similar, (including HOX genes upregulation). At 62 months of median follow-up, the 3-year overall survival (OS) for t-NPM1 AML (n = 96), dn-NPM1 AML (n = 2394), and t-AML (n = 390) were 54%, 60%, and 31%, respectively. In multivariable analysis, OS was similar for the NPM1-mutated groups (hazard ratio [HR] 0.9; 95% confidence interval [CI], 0.65-1.25; P = .45), but better in t-NPM1 AML than in t-AML (HR, 1.86; 95% CI, 1.30-2.68; P < .001). Relapse-free survival was similar between t-NPM1 and dn-NPM1 AML (HR, 1.02; 95% CI, 0.72-1.467; P = .90), but significantly higher in t-NPM1 AML versus t-AML (HR, 1.77; 95% CI, 1.19-2.64; P = .0045). t-NPM1 and dn-NPM1 AML have overlapping features, suggesting that they should be classified as a single disease entity.
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- 2022
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26. Intermediate-dose cytarabine or standard-dose cytarabine plus single-dose anthracycline as post-remission therapy in older patients with acute myeloid leukemia: impact on health care resource consumption and outcomes
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François Vergez, Suzanne Tavitian, Audrey Bidet, Pierre-Yves Dumas, Jean-Philippe Vial, Anne-Charlotte de Grande, Sarah Bertoli, Nicolas Lechevalier, Arnaud Pigneux, Emilie Klein, Isabelle Luquet, Jean Galtier, Emilie Bérard, Thibaut Leguay, Eric Delabesse, Christian Recher, Camille Alric, Audrey Sarry, and Jean Baptiste Rieu
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Male ,Oncology ,medicine.medical_specialty ,Anthracycline ,Acute myeloid leukaemia ,Older patients ,Internal medicine ,Correspondence ,Antineoplastic Combined Chemotherapy Protocols ,Health care ,medicine ,Humans ,Anthracyclines ,Registries ,Resource consumption ,RC254-282 ,Aged ,business.industry ,Remission Induction ,Cytarabine ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Myeloid leukemia ,Hematology ,Middle Aged ,Leukemia, Myeloid, Acute ,Female ,business ,medicine.drug - Published
- 2021
27. Results of Venetoclax and Azacitidine Combination in Chemotherapy Ineligible Untreated Patients with Acute Myeloid Leukemia with IDH 1/2 Mutations
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Daniel A. Pollyea, Courtney D. Dinardo, Martha L. Arellano, Arnaud Pigneux, Walter Fiedler, Marina Konopleva, David A Rizzieri, B. Douglas Smith, Atsushi Shinagawa, Roberto M. Lemoli, Monique Dail, Yinghui Duan, Brenda J. Chyla, Jalaja Potluri, Jean A Ridgeway, and Hagop M. Kantarjian
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Abstract
Introduction Isocitrate dehydrogenase (IDH) mutations occur in ~20% of acute myeloid leukemia (AML) patients (pts) and are frequently identified in older pts. Pre-clinical data showed that cells with IDH1/2 mutation (mut) were susceptible to Venetoclax (Ven) therapy (Chan et.al., 2015). Clinical studies have demonstrated that pts with IDH1/2mut treated with Ven and azacitidine (Aza) achieved high response rates that were durable, and had longer median overall survival (mOS) (DiNardo et. al., 2020; DiNardo et. al., 2019). Herein, we further evaluated the efficacy and safety of Ven+Aza among treatment-naïve AML pts with IDH1/2 mut unfit for intensive treatment either due to comorbidities and/or age ≥ 75 yrs. Methods Data were pooled from pts enrolled in an ongoing phase 3 study (NCT02993523, data cut-off: 04Jan2020) comparing pts treated with Ven+Aza or placebo (Pbo)+Aza, and a phase 1b study (NCT02203773, data cut-off: 19Jun2019) where pts were treated with Ven+Aza. Pts on Ven+Aza received Ven 400 mg daily orally (days 1-28) and Aza (75 mg/m2; days 1-7/28-day cycle). Disease assessments were performed per modified International Working Group response criteria for AML. DNA was isolated from bone marrow aspirates collected from pts prior to the first dose of study drug and analyzed centrally. Pts with positive test results for IDH1 and 2 [RealTime IDH1 or IDH2 assay (Abbott) for phase 3 study, MyAML panel (Invivoscribe) for phase 1b study] were counted as mutation "detected"; pts with a negative test result were counted as mutation "not detected." Pts without a result either due to an inconclusive test or missing specimen were excluded from the analyses. Results IDH1/2 mut was detected in 79 pts treated with Ven+Aza and 28 pts treated with Pbo+Aza. At baseline (Ven+Aza/Pbo+Aza), median age was 76 (range: 64-90)/78 (62-90) yrs. Cytogenetic risks were intermediate: 79%/68%, and poor:21%/32%. ECOG scores were: 0-1: 56%/68% and 2-3: 44%/32%. 73%/86% had de novo AML, and 27%/14% had secondary AML. IDH1 was detected in 32/11, IDH2 in 49/18, IDH2R140 in 36/15, and IDH2R172 were detected in 13/3 pts, respectively. The median number of treatment cycles received (Ven+Aza/Pbo+Aza) by IDH1/2 pts was 8 (range: 1-37)/2.5 (1-18). Complete response (CR)+CR with partial hematologic recovery (CRh) in Ven+Aza/Pbo+Aza were 72% (95% CI: 61%-82%)/7% (1%-24%) (Table). Median time to first CR/CRh response was 1.0/2.6 months (mos), and 51%/0% achieved CR+CRh by initiation of cycle (C) 2. Median duration of response (mDoR) was 29.5 [95% CI: 16.7-not reached(NR)]/15.5 (NR-NR) mos and mOS was 24.5 [15.2- NR/6.2 (2.3-12.7) mos. The separation of 95% CIs for mOS indicate superior treatment effect of Ven+Aza (Figure). In pts with IDH1, CR+CRh (Ven+Aza/Pbo+Aza) was 59%/9%. Median time to first CR/CRh response was 2.3/3.1 mos, and 25%/0% achieved CR+CRh by initiation of C2. Median DoR and OS were 21.9 (7.8-29.5)/NR and 17.5 (6.3-32.7)/2.2(1.1-5.6) mos. In pts with IDH2, CR+CRh rates were 80%/6%. Median time to first CR/CRh response was 1.0/2.1 mos and 67%/0% achieved CR+CRh by initiation of C2. Median DoR was NR (16.7-NR)/15.5 (NR-NR), and mOS was NR (17.6-NR)/13.0 (95% CI: 3.8-15.8) mos. In pts with IDH2R140, CR+CRh were 75%/7%. Median time to first CR/CRh response was 1.0/2.1 mos, and 58%/0% achieved CR+CRh by initiation of C2. Median DoR and mOS were NR (17.8-NR)/15.5 (NR-NR) and NR (15.0-NR)/12.7 (1.7-15.8) mos, respectively. Response rates in pts with IDH2R172 were 92%/0%. Median time to first CR/CRh response was 1.0/NR mos, and 92%/0% achieved response by initiation of C2. Median DoR and mOS were 16.7 (7.5-NR)/3.5 (NR-NR) and NR (12.2-NR)/13.7 (10.6-NR) mos. IDH1/2 mut pts achieved higher CR+CRh rates with Ven+Aza treatment as compared to pts with IDH not detected (72%/60%). Median DoR and mOS were 29.5 (16.7-NR)/17.5 (10.6-23.5) and 24.5 (15.2-NR)/12.3 (9.7-14.8) mos, respectively. In pts treated with Ven+Aza, grade 3/4 hematologic adverse events (AEs) among pts with IDH1/2 detected/IDH not detected were similar (81%/74%) and included grade 3/4 thrombocytopenia (46%/34%), febrile neutropenia (43%/41%), neutropenia (35%/33%) and anemia (29%/24%). Conclusion Ven+Aza compared to Aza monotherapy resulted in higher response rates, longer DoR, and mOS among treatment-naïve pts with IDH1/2mut ineligible for intensive chemotherapy. The safety profile was acceptable. No unexpected toxicities were noted with Ven+Aza combination. Disclosures Pollyea: Pfizer: Consultancy; Glycomimetics: Other; Takeda: Consultancy; Daiichi Sankyo: Consultancy; Abbvie: Consultancy, Research Funding; Syros: Consultancy; Syndax: Consultancy; Karyopharm: Consultancy; Novartis: Consultancy; Genentech: Consultancy; Amgen: Consultancy; Janssen: Consultancy; 47: Consultancy, Research Funding; Agios: Consultancy; Celgene/BMS: Consultancy. Dinardo:Notable Labs: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Agios: Consultancy, Research Funding; Celgene: Research Funding; Calithera: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Novartis: Consultancy; AbbVie: Consultancy, Research Funding; ImmuneOnc: Honoraria. Arellano:Gilead Sciences, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Hanmi: Research Funding; Cephalon Oncology: Research Funding. Fiedler:Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accomodations; Gilead: Honoraria; BMS: Honoraria; BerGenBio ASA: Research Funding; Servier: Honoraria, Other; Ariad/Incyte: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support in medical writing; Daiichi Sankyo Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accomodations; Morphosys: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support in medical writing; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accomodations, support in medical writing, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Konopleva:Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical; Calithera: Research Funding; AbbVie: Consultancy, Research Funding; Cellectis: Research Funding; AstraZeneca: Research Funding; Eli Lilly: Research Funding; Sanofi: Research Funding; Stemline Therapeutics: Consultancy, Research Funding; Agios: Research Funding; Ascentage: Research Funding; Ablynx: Research Funding; F. Hoffmann La-Roche: Consultancy, Research Funding; Amgen: Consultancy; Genentech: Consultancy, Research Funding; Kisoji: Consultancy; Rafael Pharmaceutical: Research Funding; Forty-Seven: Consultancy, Research Funding. Rizzieri:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; abbvie: Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Acrobiotech: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees; Mustang: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Smith:Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Shinagawa:AbbVie: Research Funding. Lemoli:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BerGenBio ASA: Research Funding; Celgene: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Dail:Genentech: Current Employment, Current equity holder in publicly-traded company. Duan:AbbVie: Current Employment, Other: may hold stock or options. Chyla:AbbVie: Current Employment, Current equity holder in publicly-traded company. Potluri:AbbVie: Current Employment, Other: may hold stock or stock options. Ridgeway:AbbVie: Current Employment, Current equity holder in publicly-traded company. Kantarjian:Janssen: Honoraria; Daiichi-Sankyo: Honoraria, Research Funding; Adaptive biotechnologies: Honoraria; Oxford Biomedical: Honoraria; Abbvie: Honoraria, Research Funding; Ascentage: Research Funding; Amgen: Honoraria, Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Delta Fly: Honoraria; BMS: Research Funding; Aptitute Health: Honoraria; Novartis: Honoraria, Research Funding; BioAscend: Honoraria; Jazz: Research Funding; Pfizer: Honoraria, Research Funding; Immunogen: Research Funding.
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- 2020
28. AML-108 SELECT-AML-1 Trial in Progress: A Phase 2 Study of Tamibarotene in Combination With Venetoclax and Azacitidine in Previously Untreated Adult Patients Selected for RARA-Positive AML who are Ineligible for Standard Induction Therapy
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Suman Kambhampati, Alireza Eghtedar, Christine McMahon, Stephane de Botton, Arnaud Pigneux, Brian Ball, Gautam Borthakur, Angela Volkert, Joanie Aasen Gausman, Kristen Baker, Graeme Hodgson, Erica Warlick, David Roth, Michael Kelly, Daniel Pollyea, and Eytan Stein
- Subjects
Cancer Research ,Oncology ,Hematology - Published
- 2022
29. Poster: AML-108 SELECT-AML-1 Trial in Progress: A Phase 2 Study of Tamibarotene in Combination With Venetoclax and Azacitidine in Previously Untreated Adult Patients Selected for RARA-Positive AML who are Ineligible for Standard Induction Therapy
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Suman Kambhampati, Alireza Eghtedar, Christine McMahon, Stephane de Botton, Arnaud Pigneux, Brian Ball, Gautam Borthakur, Angela Volkert, Joanie Aasen Gausman, Kristen Baker, Graeme Hodgson, Erica Warlick, David Roth, Michael Kelly, Daniel Pollyea, and Eytan Stein
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Cancer Research ,Oncology ,Hematology - Published
- 2022
30. Characteristics and clinical outcomes of SARS-CoV-2 infection in adult patients with acute leukemia in France
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Pierre-Yves, Dumas, Sarah, Bertoli, Caroline, Bonmati, Martin, Carre, Juliette, Lambert, Mario, Ojeda-Uribe, Sylvain, Chantepie, Franciane, Paul, Eric, Jourdan, Stéphanie, Haiat, Emmanuelle, Tavernier, Pierre, Peterlin, Jean-Pierre, Marolleau, Kamel, Laribi, Corentin, Orvain, Quentin, Cabrera, Pascal, Turlure, Stéphane, Girault, Marie, Balsat, Marc, Bernard, Marie-Christine, Bene, Arnaud, Pigneux, Hervé, Dombret, and Christian, Récher
- Subjects
Adult ,Leukemia, Myeloid, Acute ,Cancer Research ,Oncology ,SARS-CoV-2 ,Acute Disease ,COVID-19 ,Humans ,France ,Hematology - Published
- 2022
31. Conventional chemotherapy for acute myeloid leukemia in older adults: Impact on nutritional, cognitive, and functional status
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Christian Recher, Eric Jourdan, Anne Banos, Claire Jouzier, Franciane Paul, Bruno Lioure, Romain Guieze, Norbert Ifrah, Pierre-Yves Dumas, Caroline Bonmati, Arnaud Pigneux, Jean-François Hamel, Mathilde Hunault, Jean-Yves Cahn, Jean-Christophe Ianotto, Mario Ojeda-Uribe, Marc Bernard, Norbert Vey, Marie-Christine Béné, Hacene Zerazhi, Jacques Delaunay, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Clermont-Ferrand, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), 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), CHU Strasbourg, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Henri Duffaut (Avignon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), and 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)
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Male ,Activities of daily living ,MESH: Cognition ,0302 clinical medicine ,Cognition ,MESH: Aged, 80 and over ,Nutritional status ,Activities of Daily Living ,Prospective Studies ,MESH: Geriatric Assessment ,Aged, 80 and over ,MESH: Aged ,Cognitive status ,MESH: Middle Aged ,Myeloid leukemia ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,General Medicine ,MESH: Follow-Up Studies ,Middle Aged ,MESH: Nutritional Status ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,Older adults ,Cohort ,Toxicity ,Functional status ,Female ,MESH: Leukemia, Myeloid, Acute ,medicine.medical_specialty ,Context (language use) ,Antineoplastic Agents ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,neoplasms ,Aged ,Acute myeloid leukemia ,MESH: Humans ,business.industry ,MESH: Activities of Daily Living ,Geriatric assessment ,MESH: Male ,MESH: Prospective Studies ,MESH: Antineoplastic Agents ,business ,MESH: Female ,030215 immunology ,Follow-Up Studies - Abstract
International audience; Objectives: The impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of elderly patients is seldom studied. This assessment was performed in the context of the LAMSA 2007 trial.Methods: The trial enrolled 424 patients with de novo AML. Among them, 316 benefited from geriatric assessment (GA) including nutritional, cognitive, and functional status and were scored according to Eastern Cooperative Oncology Group (ECOG) and sorror for the prediction of treatment toxicity, morbidity, and mortality. Patients were investigated at diagnosis for three times during follow-up.Results: This study showed that AML and its treatment have no impact on cognitive (P = .554) nor functional status (P = .842 for Activity of Daily Living and P = .087 for Instrumental Activities of Daily Living). The nutritional status improved over time (P = .041). None of these three parameters at baseline, associated or not with ECOG and sorror scores, impacted survivals or toxicities.Conclusions: The cognitive, functional, and nutritional status had no impact in this cohort of fit elderly AML patients without unfavorable cytogenetics. The GA tools used provided no additional information compared with ECOG and sorror scores, to predict toxicity, morbidity, or mortality due to intensive chemotherapy.
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- 2021
32. Outcome after hematopoietic stem cell transplantation in patients with extranodal natural killer/T-Cell lymphoma, nasal type: A French study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
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Phong-Dinh Nguyen, Lucile Couronné, Arnaud Jaccard, Olivier Hermine, Société Française de Greffe de Moelle et de Thérapie Cellulaire, Mohamad Mohty, Patrice Chevallier, Laure Philippe Walter, Ibrahim Yakoub-Agha, Régis Peffault de Latour, Nathalie Fegueux, Catherine Thieblemont, Emmanuel Bachy, Arnaud Pigneux, Jean-Philippe Jais, Didier Blaise, Gérard Socié, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Oncology ,Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Nose Neoplasms ,Graft vs Host Disease ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Hematopoietic stem cell transplantation ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,ComputingMilieux_MISCELLANEOUS ,Aged ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,Hematology ,Middle Aged ,medicine.disease ,Natural killer T cell ,Prognosis ,Progression-Free Survival ,Lymphoma ,Transplantation ,Radiation therapy ,Lymphoma, Extranodal NK-T-Cell ,Treatment Outcome ,030220 oncology & carcinogenesis ,Cohort ,Female ,France ,Stem cell ,business ,030215 immunology - Abstract
We evaluated the outcome of 65 French patients with Extranodal NK/T-cell lymphoma, nasal type (ENKTL) undergoing haematopoietic stem cell transplantation (HSCT) (19 allogeneic and 46 autologous). Fifty-four patients (83%), most of which receiving L asparaginase (L-aspa) containing regimens (81%), achieved complete or partial response at time of HCST. After a median follow-up of 79.9 months, 4-years progression-free survival (PFS) and overall survival (OS) were similar in both autologous and allogeneic groups (PFS: 34% vs 26%, p=0.12 and OS: 52% vs 53%, p=0.74). Response status at HSCT was the major independent prognostic factor on survival (OS: HR: 4.013 [1.137; 14.16], p=0.031 and PFS: HR: 5.231 [1.625; 16.838], p=0.006). As compared to control patients receiving chemotherapy and/or radiotherapy containing regimens only, upfront HSCT did not improve the outcome of responder patients, including those treated by L-aspa. However, it tends to provide survival benefit for relapsed patients with initial high-risk clinical features who achieved second remission. Whereas the place of HSCT in upfront therapy has still to be clarified, these data confirm that HSCT should be considered for consolidation in selected patients with relapsed ENKTL. Based on a large non Asian ENKTL cohort since the L-aspa era, this study provides some insight into the survival patterns of ENKTL patients with HSCT in the Western hemisphere and may give future direction for the next clinical trial design. This article is protected by copyright. All rights reserved.
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- 2021
33. Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial
- Author
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Norbert Ifrah, Hacene Zerazhi, Pierre-Yves Dumas, Norbert Vey, Isabelle Luquet, Denis Caillot, Marie-Christine Béné, Célestine Simand, Marie-Pierre Ledoux, Véronique Dorvaux, Yosr Hicheri, Anne Banos, Maria Pilar Gallego Hernanz, Chantal Himberlin, Odile Blanchet, Eric Delabesse, Catherine Humbrecht, Pascal Turlure, Arnaud Pigneux, Eric Jourdan, Jacques Delaunay, Didier Bouscary, Emmanuelle Tavernier, Christian Recher, Gaelle Guillerm, Mathilde Hunault-Berger, Romain Guieze, Martin Carre, Anne Bouvier, Jean-Pierre Marolleau, Claude Eric Bulabois, Pascale Cornillet-Lefebvre, Mario Ojeda-Uribe, Marc Bernard, Magda Alexis, Jean-François Hamel, Etienne Daguindau, Pierre Peterlin, Gabrielle Roth Guepin, Emmanuel Gyan, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), 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), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital privé du Confluent [Nantes], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), 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 Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France., Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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 de Nancy (CHRU Nancy), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Reims (CHU Reims), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang [Angers], CHU Pontchaillou [Rennes], Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), 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 d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Henri Duffaut (Avignon), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), 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), Centre de Ressources Biologiques [CHU Angers], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Subjects
Oncology ,Adult ,Male ,Risk ,medicine.medical_specialty ,NPM1 ,Adolescent ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,DNA Mutational Analysis ,Phases of clinical research ,Gene mutation ,Disease-Free Survival ,Cytogenetics ,Young Adult ,Internal medicine ,hemic and lymphatic diseases ,CEBPA ,Medicine ,Cluster Analysis ,Humans ,Chemotherapy ,business.industry ,Gene Expression Regulation, Leukemic ,Gene Expression Profiling ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,Gemtuzumab ,Transplantation ,Leukemia, Myeloid, Acute ,Karyotyping ,Cytogenetic Analysis ,Mutation ,Female ,business - Abstract
International audience; In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m(2) of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (
- Published
- 2021
34. Data from French named patient program of quizartinib in relapsed/refractory acute myeloid leukemia
- Author
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Anne Banos, Stefan Wickenhauser, Fabrice Larosa, Filo, R. Redjoul, Pierre-Yves Dumas, Nolwenn Lucas, Jamile Frayfer, Martin Carre, M. Alexis, M. Elassy, Arnaud Pigneux, Emmanuel Raffoux, Pierre Peterlin, Marie-Virginie Larcher, N. Maillard, Christian Recher, J. Michel, J. B. Mear, M. Detrait, V. Morel, Sylvain Chantepie, Mario Ojeda-Uribe, Y. Desbrosses, S. Fodil, Celia Salanoubat, Hervé Dombret, Thomas Cluzeau, C. Mediavilla, Sarah Bertoli, Driss Chaoui, Mathilde Hunault-Berger, and V. Vidal
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Text mining ,Internal medicine ,medicine ,Overall survival ,Humans ,Benzothiazoles ,Quizartinib ,Chemotherapy ,business.industry ,Phenylurea Compounds ,Hazard ratio ,Myeloid leukemia ,Hematology ,Leukemia, Myeloid, Acute ,chemistry ,fms-Like Tyrosine Kinase 3 ,030220 oncology & carcinogenesis ,Relapsed refractory ,business ,030215 immunology ,Chemotherapy group - Abstract
Quizartinib improved outcome compared to chemotherapy in the QuANTUM-R study (median overall survival (OS): 6.2 months for quizartinib vs. 4.7 in the chemotherapy group; hazard ratio 0.76, p = 0.02...
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- 2021
35. In-depth time-dependent analysis of the benefit of allo-HSCT for elderly patients with CR1 AML: a FILO study
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Alice Garnier, Gaelle Guillerm, Anne Bouvier, Patrice Ceballos, Marie C. Béné, Yosr Hicheri, Arnaud Pigneux, Christian Recher, Mathilde Hunault-Berger, Sarah Guenounou, Raynier Devillier, Patrice Chevallier, Anne Huynh, Edouard Forcade, Pierre-Yves Dumas, Sylvain Thepot, Didier Blaise, Pierre Peterlin, Norbert Vey, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Association internationale pour le développement de l’agroenvironnement (AIDA), 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 de Brest (CHRU Brest), Hôpital Lapeyronie [Montpellier] (CHU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique et Thérapie Cellulaire [CHU Bordeaux], Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux], Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), 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 [Institut Paoli Calmettes, Marseille], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d’Oncologie Médicale [IPC, Marseille], and Institut National de la Santé et de la Recherche Médicale (INSERM)
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Oncology ,medicine.medical_specialty ,Multivariate analysis ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Allo hsct ,Hematopoietic stem cell transplantation ,European LeukemiaNet ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Aged ,Proportional Hazards Models ,business.industry ,Hazard ratio ,Remission Induction ,Complete remission ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Middle Aged ,medicine.disease ,Leukemia ,Leukemia, Myeloid, Acute ,Receptors, Complement 3b ,business - Abstract
The benefit of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute myeloid leukemia (AML) aged >60 years remains a matter of debate, notably when performed in first complete remission (CR1). To clarify this issue, the French Innovative Leukemia Organization (FILO) performed a 10-year real-world time-dependent analysis. The study enrolled patients between 60 and 70 years of age with AML in CR1 after intensive chemotherapy with intermediate (IR) or unfavorable (UR) risk according to the European LeukemiaNet (ELN) 2010 classification. The impact of allo-HSCT was analyzed through three models: (1) time-dependent Cox; (2) multistate for dynamic prediction; and (3) super landmark. The study enrolled 369 (73%) IR and 138 (27%) UR patients with AML, 203 of whom received an allo-HSCT. Classical multivariate analysis showed that allo-HSCT significantly improved relapse-free survival (RFS; hazard ratio [HR] [95% confidence interval (CI)], 0.47 [0.35-0.62]; P < .001) and overall survival (OS; HR [95% CI], 0.56 [0.42-0.76]; P < .001), independently of the ELN risk group. With the multistate model, the predicted 5-year probability for IR and UR patients to remain in CR1 without allo-HSCT was 8% and 1%, respectively. Dynamic predictions confirmed that patients without allo-HSCT continue to relapse over time. Finally, the super landmark model showed that allo-HSCT significantly improved RFS (HR [95% CI], 0.47 [0.36-0.62]; P < .001) and OS (HR [95% CI], 0.54 [0.40-0.72]; P < .001). allo-HSCT in CR1 is reported here as significantly improving the outcome of fit older patients with AML. Long-term RFS without allo-HSCT is very low (
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- 2021
36. MDS-335: Ivosidenib (IVO) in Patients with IDH1-Mutant Relapsed/Refractory Myelodysplastic Syndrome (R/R MDS): Updated Enrollment for the MDS Sub-Study
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Vickie Zhang, Xavier Thomas, James M. Foran, Stéphane de Botton, Martha Arellano, Amir T. Fathi, Justin M. Watts, Richard Stone, Courtney D. DiNardo, Harry P. Erba, Guillermo Garcia-Manero, Ian R Lemieux, Geoffrey L. Uy, Gail J. Roboz, Eytan M. Stein, Robert K. Stuart, Anthony S. Stein, Arnaud Pigneux, Gabrielle T. Prince, David A. Sallman, Stephanie M. Kapsalis, and Prapti A. Patel
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Cancer Research ,Cytopenia ,medicine.medical_specialty ,business.industry ,Induction chemotherapy ,Context (language use) ,Hematology ,medicine.disease ,Discontinuation ,Clinical trial ,Oncology ,Tolerability ,hemic and lymphatic diseases ,Pharmacodynamics ,Internal medicine ,medicine ,Adverse effect ,business - Abstract
Context: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in ~3% of patients with MDS and are associated with increased transformation to acute myeloid leukemia (AML). IVO is an oral, potent, targeted inhibitor of the mutant IDH1 (mIDH1) enzyme and is FDA-approved for mIDH1 R/R AML and mIDH1 newly diagnosed AML in patients ≥75 years old or with comorbidities precluding the use of intensive induction chemotherapy. In the first-in-human, phase 1 study of IVO in patients with mIDH1 advanced hematologic malignancies (NCT02074839), 12 patients with R/R MDS, with median age 72.5 years (range 52–78), received IVO 500 mg once daily (QD). All patients received prior MDS treatment. Investigator-assessed ORR (CR + PR + marrow CR, per IWG 2006) was 75% (95% CI 43–95), with median duration of response of 21.4 months (95% CI 2.3–NE). Nine (75%) patients were transfusion-independent for ≥56 days during treatment. No dose-limiting toxicities or adverse events leading to treatment discontinuation were reported among patients with MDS. Based on these encouraging data, the FDA granted Breakthrough Therapy Designation to IVO in mIDH1 MDS; the study was amended to enroll additional patients with mIDH1 R/R MDS. Objective: To evaluate safety, tolerability, clinical activity, and pharmacokinetics/pharmacodynamics of IVO in patients with mIDH1 R/R MDS. Design: A sub-study of the single-arm, open-label, phase 1 dose escalation and expansion study of IVO in mIDH1 advanced hematologic malignancies, evaluating patients with R/R MDS. Patients must have R/R disease after prior standard therapy; high disease burden based on cytopenia and/or transfusion dependence at baseline; an Eastern Cooperative Oncology Group performance status score of 0–2; and be amenable to bone marrow aspirate and/or core biopsy at specified study timepoints. Patients with documented AML are not eligible. IVO 500 mg QD orally on days 1–28 of 28-day cycles. Results: Study is open; enrollment of ~23 patients from the US and France planned. Results not yet available. Conclusions: This sub-study will provide additional insights into safety, tolerability, clinical activity, and pharmacokinetics/pharmacodynamics of treatment with IVO in patients with mIDH1 R/R MDS. Funding: Agios; Servier.
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- 2021
37. Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort
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Patrice Chevallier, Alexis Caulier, Gabrielle Roth-Guepin, Xavier Thomas, Pierre-Yves Dumas, Yosr Hicheri, Florence Pasquier, Sarah Bertoli, Jean-Baptiste Micol, Edmond Chiche, Thomas Cluzeau, Ramy Rahmé, Arnaud Pigneux, Magalie Joris, Patrick Auberger, Pierre Peterlin, Caroline Lejeune, Ollivier Legrand, Mohamad Mohty, Norbert Vey, Caroline Bonmati, Lionel Ades, Michael Loschi, Christian Recher, Emmanuel Raffoux, Alexis Genthon, Université Côte d'Azur - Faculté de Médecine (UCA Faculté Médecine), Université Côte d'Azur (UCA), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), 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), CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France., BMGIC, U1035 INSERM, University of Bordeaux, Bordeaux, France, Cellules souches hématopoïétiques et développement des hémopathies myéloïdes (CSHMyelo), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Saint-Eloi, CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'Hématologie, CHU Nice, 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), 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 - Faculté de Médecine (SU FM), Sorbonne Université (SU), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Hopital Saint-Louis [AP-HP] (AP-HP), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University of Lausanne (UNIL), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-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)-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), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Institut Gustave Roussy (IGR), Université Paris-Saclay, Département d'hématologie [Gustave Roussy], Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Université Paris Cité (UPCité), and DESSAIVRE, Louise
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Adult ,Oncology ,medicine.medical_specialty ,Multivariate analysis ,Daunorubicin ,[SDV]Life Sciences [q-bio] ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Aged ,Retrospective Studies ,Response rate (survey) ,Myeloid Neoplasia ,business.industry ,Cytarabine ,Myeloid leukemia ,Hematology ,Minimal residual disease ,Transplantation ,[SDV] Life Sciences [q-bio] ,Leukemia, Myeloid, Acute ,Cohort ,business ,medicine.drug - Abstract
CPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). We retrospectively analyzed the efficacy and safety of CPX-351 in a real-world setting in 103 patients from 12 French centers, including the evaluation of molecular abnormalities at baseline and minimal residual disease (MRD) in responding patients, compared with a historical data set from Bordeaux-Toulouse DATAML registry. A favorable safety profile was observed, with a low frequency of alopecia (11%) and gastrointestinal toxicity (50%). The overall response rate after induction was 59%, and MRD
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- 2021
38. Prognostic significance of concurrent gene mutations i n intensively treated patients with IDH-mutated AML: an ALFA study
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Céline Berthon, Lionel Ades, Nicolas Boissel, Emilie Lemasle, Christian Recher, Xavier Thomas, Nicolas Duployez, Norbert Vey, Raphael Itzykson, Sylvain Chantepie, Karine Celli-Lebras, Arnaud Pigneux, Pascal Turlure, Stéphane de Botton, Claude Preudhomme, Claude Gardin, Denis Caillot, Jean-Pierre Marolleau, Christine Terré, Jean-Baptiste Micol, Hervé Dombret, Thorsten Braun, Juliette Lambert, Emmanuel Raffoux, Jean-Valère Malfuson, Matthieu Duchmann, Cécile Pautas, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Université Paris-Saclay, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Amiens-Picardie, Hôpital Avicenne [AP-HP], Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Hôpital Henri Mondor, Centre Hospitalier de Versailles André Mignot (CHV), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Cellules souches hématopoïétiques et développement des hémopathies myéloïdes (CSHMyelo), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 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), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Institut d'Hématologie de Basse-Normandie (IHBN), 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)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Centre de Transfusion Sanguine des Armées (CTSA), Service d'hématologie clinique, 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 Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Universitaire d'Hématologie (IUH), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [CHU Toulouse], CHU Toulouse [Toulouse], and DESSAIVRE, Louise
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Male ,Oncology ,medicine.medical_specialty ,NPM1 ,IDH1 ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Immunology ,Abnormal Karyotype ,Hematopoietic stem cell transplantation ,Gene mutation ,medicine.disease_cause ,Biochemistry ,Disease-Free Survival ,DNA Methyltransferase 3A ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Point Mutation ,Medicine ,Prospective Studies ,In Situ Hybridization, Fluorescence ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Chromosome Aberrations ,Clinical Trials as Topic ,Mutation ,Acute leukemia ,business.industry ,Myeloid leukemia ,Cell Biology ,Hematology ,Middle Aged ,Isocitrate Dehydrogenase ,Neoplasm Proteins ,[SDV] Life Sciences [q-bio] ,Leukemia, Myeloid, Acute ,Isocitrate dehydrogenase ,Female ,France ,business ,Nucleophosmin - Abstract
International audience; In patients with isocitrate dehydrogenase (IDH)-mutated acute myeloid leukemia (AML) treated by intensive chemotherapy (IC), prognostic significance of co-occurring genetic alterations and allogeneic hematopoietic stem cell transplantation (HSCT) are of particular interest with the advent of IDH1/2 mutant inhibitors. We retrospectively analyzed 319 patients with newly diagnosed AML (127 with IDH1, 135 with IDH2R140, and 57 with IDH2R172 mutations) treated with IC in 3 Acute Leukemia French Association prospective trials. In each IDH subgroup, we analyzed the prognostic impact of clinical and genetic covariates, and the role of HSCT. In patients with IDH1 mutations, the presence of NPM1 mutations was the only variable predicting improved overall survival (OS) in multivariate analysis (P< .0001). In IDH2R140-mutated AML, normal karyotype (P = .008) and NPM1 mutations (P = .01) predicted better OS. NPM1 mutations were associated with better disease-free survival (DFS; P = .0009), whereas the presence of DNMT3A mutations was associated with shorter DFS (P = .0006). In IDH2R172-mutated AML, platelet count was the only variable retained in the multivariate model for OS (P = .002). Among nonfavorable European LeukemiaNet 2010-eligible patients, 71 (36%) underwent HSCT in first complete remission (CR1) and had longer OS (P = .03) and DFS (P = .02) than nontransplanted patients. Future clinical trials testing frontline IDH inhibitors combined with IC may consider stratification on NPM1 mutational status, the primary prognostic factor in IDH1- or IDH2R140-mutated AML. HSCT improve OS of nonfavorable IDH1/2-mutated AML and should be fully integrated into the treatment strategy.
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- 2021
39. A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia
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Norbert Vey, Mauricette Michallet, Sylvain Chantepie, Xavier Thomas, Paul-Arthur Meslin, Delphine Lebon, Christine Terré, Sylvie Chevret, Claude Preudhomme, Pascal Turlure, Emilie Lemasle, Sébastien Maury, Emmanuel Raffoux, Karine Celli-Lebras, Nicolas Duployez, Pierre-Yves Dumas, Raphael Itzykson, Céline Berthon, Jean-Valère Malfuson, Denis Caillot, Arnaud Pigneux, Ibrahim Yakoub-Agha, Juliette Lambert, Auriane Lesieur, Christian Recher, Claude Gardin, Pierre Sujobert, Cécile Pautas, Benoît Ducourneau, Gérard Socié, Gael Fortin, Stéphanie Nguyen, Laurène Fenwarth, Stéphane de Botton, Hervé Dombret, Nicolas Boissel, Jean-Henri Bourhis, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France., Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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 Léon Bérard [Lyon], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut d'Hématologie de Basse-Normandie (IHBN), 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)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Hôpital Avicenne [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de Transfusion Sanguine des Armées (CTSA), Service de Santé des Armées, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Henri Mondor [Créteil], Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), DESSAIVRE, Louise, Centre International des greffes [CHU Saint-Antoine] (EBMT), 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), CHU Henri Mondor, Service d'Hématologie [CHU Toulouse], and CHU Toulouse [Toulouse]
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Oncology ,Male ,Myeloid ,Neoplasm, Residual ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Datasets as Topic ,Hematopoietic stem cell transplantation ,Biochemistry ,European LeukemiaNet ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Multicenter Studies as Topic ,Precision Medicine ,Randomized Controlled Trials as Topic ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Nuclear Proteins ,Hematology ,Middle Aged ,Prognosis ,Combined Modality Therapy ,[SDV] Life Sciences [q-bio] ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,surgical procedures, operative ,Female ,Nucleophosmin ,Algorithms ,Adult ,medicine.medical_specialty ,NPM1 ,Adolescent ,Immunology ,Clinical Decision-Making ,Risk Assessment ,Young Adult ,Clinical Trials, Phase II as Topic ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,business.industry ,Cell Biology ,Models, Theoretical ,medicine.disease ,Minimal residual disease ,Transplantation ,business - Abstract
A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome predictions and tailor therapeutic decisions, including hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). We assessed the performance of the KB in guiding HSCT decisions in first complete remission (CR1) in 656 AML patients younger than 60 years from the ALFA-0702 trial (NCT00932412). KB predictions of overall survival (OS) were superior to those of European LeukemiaNet (ELN) 2017 risk stratification (C-index, 68.9 vs 63.0). Among patients reaching CR1, HSCT in CR1, as a time-dependent covariate, was detrimental in those with favorable ELN 2017 risk and those with negative NPM1 minimal residual disease (MRD; interaction tests, P = .01 and P = .02, respectively). Using KB simulations of survival at 5 years in a scenario without HSCT in CR1 (KB score), we identified, in a similar time-dependent analysis, a significant interaction between KB score and HSCT, with HSCT in CR1 being detrimental only in patients with a good prognosis based on KB simulations (KB score ≥40; interaction test, P = .01). We could finally integrate ELN 2017, NPM1 MRD, and KB scores to sort 545 CR1 patients into 278 (51.0%) HSCT candidates and 267 (49.0%) chemotherapy-only candidates. In both time-dependent and 6-month landmark analyses, HSCT significantly improved OS in HSCT candidates, whereas it significantly shortened OS in chemotherapy-only candidates. Integrating KB predictions with ELN 2017 and MRD may thus represent a promising approach to optimize HSCT timing in younger AML patients.
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- 2021
40. Publisher Correction: Outcome of older (=70 years) APL patients frontline treated with or without arsenic trioxide-an International Collaborative Study
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Sabine Kayser, Marta Sobas, Olga Salamero, Cristina Gil, Uwe Platzbecker, Richard F. Schlenk, Gabriel Ghiaur, Javier de la Serna, Mar Tormo, David Martínez-Cuadrón, Mark J. Levis, Miguel A. Sanz, Emmanuel Raffoux, Eva Lengfelder, Norbert Vey, Pierre Fenaux, Arnaud Pigneux, Agnès Guerci-Bresler, Ana Garrido, Xavier Thomas, Pau Montesinos, Lionel Adès, and Ramy Rahmé
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Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,Outcome (game theory) ,Acute myeloid leukaemia ,chemistry.chemical_compound ,Text mining ,Oncology ,chemistry ,Internal medicine ,medicine ,Clinical genetics ,Arsenic trioxide ,business - Published
- 2021
41. Allogeneic hematopoietic stem cell transplantation for adult patients with t(4;11)(q21;q23) KMT2A/AFF1 B-cell precursor acute lymphoblastic leukemia in first complete remission: impact of pretransplant measurable residual disease (MRD) status. An analysis from the Acute Leukemia Working Party of the EBMT
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Gérard Socié, Jordi Esteve, Christoph Schmid, Jan J. Cornelissen, Tomasz Czerw, Arnaud Pigneux, Ibrahim Yakoub-Agha, Sebastian Giebel, Vladimir Koza, Hélène Labussière-Wallet, Nigel H. Russell, Depei Wu, Avichai Shimoni, Mohamad Mohty, Patrice Chevallier, Arnon Nagler, Myriam Labopin, Zinaida Peric, Liisa Volin, Anton Schattenberg, Rainer Schwerdtfeger, Robin Foà, Johan Maertens, and Hematology
- Subjects
0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Neoplasm, Residual ,Transplantation Conditioning ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Translocation, Genetic ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,hemic and lymphatic diseases ,Internal medicine ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Medicine ,Humans ,Transplantation, Homologous ,Survival rate ,B cell ,Retrospective Studies ,Acute leukemia ,biology ,business.industry ,Chromosomes, Human, Pair 11 ,Hazard ratio ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,Hematology ,Histone-Lysine N-Methyltransferase ,Prognosis ,Transplantation ,DNA-Binding Proteins ,Survival Rate ,030104 developmental biology ,KMT2A ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Chromosomes, Human, Pair 4 ,Transcriptional Elongation Factors ,business ,Myeloid-Lymphoid Leukemia Protein ,Follow-Up Studies - Abstract
Adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with t(4;11)(q21;q23);KMT2A/AFF1 is a poor-prognosis entity. This registry-based study was aimed to analyze outcome of patients with t(4;11) BCP-ALL treated with allogeneic hematopoietic stem cell transplantation (alloHSCT) in first complete remission (CR1) between 2000 and 2017, focusing on the impact of measurable residual disease (MRD) at the time of transplant. Among 151 patients (median age, 38) allotransplanted from either HLA-matched siblings or unrelated donors, leukemia-free survival (LFS) and overall survival (OS) at 2 years were 51% and 60%, whereas relapse incidence (RI) and non-relapse mortality (NRM) were 30% and 20%, respectively. These results were comparable to a cohort of contemporary patients with diploid normal karyotype (NK) BCP-ALL with equivalent inclusion criteria (n = 567). Among patients with evaluable MRD pre-alloHSCT, a negative status was the strongest beneficial factor influencing LFS (hazard ratio [HR] = 0.2, p < 0.001), OS (HR = 0.14, p < 0.001), RI (HR = 0.23, p = 0.001), and NRM (HR = 0.16, p = 0.002), with a similar outcome to MRD-negative NK BCP-ALL patients. In contrast, among patients with detectable pretransplant MRD, outcome in t(4;11) BCP-ALL was inferior to NK BCP-ALL (LFS: 27% vs. 50%, p = 0.02). These results support indication of alloHSCT in CR1 for t(4;11) BCP-ALL patients, provided a negative MRD status is achieved. Conversely, pre-alloHSCT additional therapy is warranted in MRD-positive patients.
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- 2020
42. Very Long Term Follow up a Phase II Study of Post-Remission Subcutaneous (SC) Azacitidine (AZA) in Patients with AML Post-MDS or Higher-Risk (HR) MDS
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Lionel Ades, Krimo Bouabdallah, Xavier Thomas, Chantal Himberlin, Denis Caillot, Emmanuel Raffoux, Amina Cherait, Agnès Guerci, Hervé Dombret, Fatiha Chermat, Arnaud Pigneux, Sylvie Chevret, Pierre Fenaux, Anne Banos, Claude Gardin, Thorsten Braun, Jean Pierre Marolleau, Norbert Vey, Cécile Pautas, Anne Laure Taksin, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), CHU Bordeaux [Bordeaux], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Amiens-Picardie, CHU Henri Mondor, Le CHCB, Centre Hospitalier de la Côte Basque, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), and DESSAIVRE, Louise
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Oncology ,medicine.medical_specialty ,Long term follow up ,business.industry ,[SDV]Life Sciences [q-bio] ,Immunology ,Azacitidine ,Phases of clinical research ,Cell Biology ,Hematology ,Biochemistry ,[SDV] Life Sciences [q-bio] ,Internal medicine ,medicine ,In patient ,business ,ComputingMilieux_MISCELLANEOUS ,medicine.drug - Abstract
Background: Results of the phase III QUAZAR trial suggest that post-remission treatment with an oral form (CC-486) of azacitidine (AZA) can prolong CR duration and overall survival(OS) in AML patients reaching at least PR with intensive chemotherapy (IC) (Wei et al, ASH 2019). Maintenance treatment with subcutaneous (SC) AZA was recently shown to improve DFS in elderly AML (Huls et al, Blood 2019, a study that also included 10% MDS). We report very long term results of a study evaluating SC AZA as post-remission treatment in patients with AML post-MDS or high-risk MDS (HR-MDS) who achieved at least PR after IC, a population known to have short responses with IC. Methods: Inclusion criteria were (1) HR-MDS according to IPSS, or AML after a documented phase of MDS(2) who entered CR, CRi or PR after IC with anthracycline and AraC within 28 days of inclusion (3) ECOG Results: From July 2006 to June 2009, 51 pts (M:31/F:20) were included. The 46 evaluable pts had achieved CR (n=28), CRi (n=11), and PR (n=7) before study entry. Median age was 66y (range 55-78). Diagnosis at IC onset was MDS (n=13) and AML (n=33), IPSS cytogenetics was normal (n= 28), intermediate (n=10), high (n= 6), and failed (n=2). Median time from diagnosis of MDS to IC was 8 months (range 0.5-101). Median number of AZA maintenance cycles was 7.5 (1-76) in CR pts (>23 cycles in 5 of them) and 4.5 (1-24) in CRi or PR pts (> 23 cycles in 1). Two patients were allografted and censored at allo SCT. Median follow-up was 16.5 months As of May 2020 (cut off date of analysis) median DFS and OS from response were 6.9 m and 16.9 m, respectively (figure). In CR patients, median and 18 months OS were 18.9 months and 58%, versus 12.8 months and 50% in CRi-PR patients (p=0.33) All non allografted patients eventually relapsed. 7 had a response duration >18 months (6 CR patients: 22, 23, 25, 36, 40, and 84 months; 1 CRi patient: 24 months) OS from inclusion was >3 years in 7 patients (CR pts: 150, 126,74, 51, 50,40 months; CRi pt:58 months), in addition to the 2 allografted pts who remained alive in CR at 156+ and 159+ months No baseline factor including cytogenetics, diagnosis at IC onset (MDS vs AML), % bone marrow blasts, age or time from MDS diagnosis to treatment, significantly predicted DFS or OS. AZA dosing in CR patients was escalated in 9 pts to 75mg/m2/d due to good tolerance but had to be reduced in 6 pts, due to GI toxicity (n=1) and cytopenias (n=5). During SC AZA maintenance, 2/28 CR pts developed febrile neutropenia, compared to 4/18 pts in CRi or PR (including 1 fatal case). In the 22 AML post MDS pts who reached CR, DFS and OS were similar to those observed in 46 AML post AML pts included in a previous ALFA study where pts in CR after IC received DNR/IDA-AraC post-remission therapy (Gardin, Blood 2007). Conclusion: In the very long term analysis of this trial in AML post MDS and HR-MDS treated with induction intensive chemotherapy, post-remission therapy with SC AZA alone was associated with a median DFS and OS of 6.9 and 16.9 months, respectively, with some prolonged response. Results appeared similar to those we had reported with intensive consolidation chemotherapy, but using an ambulatory treatment with limited myelosuppression. Figure Disclosures Braun: Daiichy-Sankyo: Honoraria; Servier: Research Funding. Bouabdallah:Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria. Ades:Celgene/BMS: Research Funding; novartis: Research Funding; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding. Fenaux:Abbvie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Jazz: Honoraria, Research Funding.
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- 2020
43. Outcome of older (≥70 years) APL patients frontline treated with or without arsenic trioxide-an International Collaborative Study
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Pierre Fenaux, Ana Garrido, David Martínez-Cuadrón, Uwe Platzbecker, Gabriel Ghiaur, Olga Salamero, Javier de la Serna, Lionel Adès, Sabine Kayser, Norbert Vey, Richard F. Schlenk, Xavier Thomas, Eva Lengfelder, Pau Montesinos, Arnaud Pigneux, Ramy Rahmé, Agnès Guerci-Bresler, Miguel A. Sanz, Marta Sobas, Cristina Gil, Mar Tormo, Mark J. Levis, Emmanuel Raffoux, Institut Català de la Salut, [Kayser S] Medical Clinic and Policlinic I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany. German Cancer Research Center (DKFZ), Heidelberg, Germany. Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany. [Rahmé R] Hôpital Saint Louis, Université Paris Diderot, Paris, France. [Martínez-Cuadrón D] Hematology Department, Hospital Universitari i Politècnic, La Fe, Avinguda Fernando Abril Martorell, 106, 46026 València, Spain. CIBERONC, Instituto Carlos III, Madrid, Spain. [Ghiaur G] Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. [Thomas X] Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre Bénite, Lyon, France. [Sobas M] Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland. [Salamero O] Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Male ,Cancer Research ,ANTHRACYCLINE MONOCHEMOTHERAPY ,Myeloid ,medicine.medical_treatment ,International Cooperation ,ACUTE PROMYELOCYTIC LEUKEMIA ,Leucèmia mieloide aguda - Quimioteràpia ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Gastroenterology ,chemistry.chemical_compound ,Remission induction ,Arsenic Trioxide ,Antineoplastic Combined Chemotherapy Protocols ,Cumulative incidence ,Arsenic trioxide ,ELDERLY-PATIENTS ,Aged, 80 and over ,ADDITIONAL CHROMOSOME-ABNORMALITIES ,Remission Induction ,Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute [DISEASES] ,Hematology ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Treatment Outcome ,Oncology ,Female ,FLT3 GENE ,Acute promyelocytic leukemia ,medicine.medical_specialty ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,ACUTE MYELOID-LEUKEMIA ,Article ,Acute myeloid leukaemia ,neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda [ENFERMEDADES] ,Internal medicine ,White blood cell ,medicine ,Humans ,Clinical genetics ,neoplasms ,CONSOLIDATION THERAPY ,Aged ,Chemotherapy ,business.industry ,organic chemicals ,diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Correction ,biochemical phenomena, metabolism, and nutrition ,Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,medicine.disease ,TANDEM DUPLICATION ,bacterial infections and mycoses ,biological factors ,RISK-ADAPTED TREATMENT ,TRANS-RETINOIC ACID ,chemistry ,Avaluació de resultats (Assistència sanitària) ,business - Abstract
Data on outcome in older (≥70 years) patients with acute promyelocytic leukemia after treatment with arsenic trioxide (ATO) compared with standard chemotherapy (CTX) is scarce. We evaluated 433 patients (median age, 73.4 years) treated either with ATO+ all-trans retinoic acid (ATO/ATRA; n = 26), CTX/ATRA + ATO during consolidation (CTX/ATRA/ATO; n = 148), or with CTX/ATRA (n = 259). Median follow-up for overall survival (OS) was 4.8 years. Complete remissions (CR) were achieved in 92% with ATO/ATRA and 82% with CTX/ATRA; induction death rates were 8% and 18%, respectively. For analysis of postremission outcomes we combined the ATO/ATRA and CTX/ATRA/ATO groups (ATO/ATRA ± CTX). Cumulative incidence of relapse (CIR) was significantly lower after ATO/ATRA ± CTX compared with CTX/ATRA (P P = 0.20). High (>10 × 109/l) white blood cell (WBC) counts at diagnosis were associated with higher CIR (P P = 0.48). ATO, when added to ATRA or CTX/ATRA is feasible and effective in elderly patients for remission induction and consolidation, particularly in patients with high WBC at diagnosis.
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- 2019
44. Arsenic trioxide is required in the treatment of newly diagnosed acute promyelocytic leukemia. Analysis of a randomized trial (APL 2006) by the French Belgian Swiss APL group
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Olivier Spertini, Xavier Thomas, Patrice Chevallier, Eric Deconinck, Lionel Adès, Norbert Vey, Tony Marchand, Julie Lejeune, Hervé Dombret, Jean Francois Lambert, Stephane Girault, Claude Gardin, Pierre Fenaux, Sylvie Chevret, Agnes Guerci Bresler, Stéphane de Botton, Emmanuel Raffoux, Arnaud Pigneux, Olivier Tournilhac, Christian Recher, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
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Adult ,Male ,Acute Myeloid Leukemia ,0301 basic medicine ,Acute promyelocytic leukemia ,medicine.medical_specialty ,Anthracycline ,medicine.medical_treatment ,chemistry.chemical_element ,Tretinoin ,Gastroenterology ,Disease-Free Survival ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Arsenic Trioxide ,Belgium ,Leukemia, Promyelocytic, Acute ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Anthracyclines ,Arsenic trioxide ,ComputingMilieux_MISCELLANEOUS ,Arsenic ,Chemotherapy ,business.industry ,Anthracyclines/administration & dosage ,Antineoplastic Combined Chemotherapy Protocols/therapeutic use ,Arsenic Trioxide/administration & dosage ,Female ,France ,Leukemia, Promyelocytic, Acute/diagnosis ,Leukemia, Promyelocytic, Acute/drug therapy ,Middle Aged ,Switzerland ,Treatment Outcome ,Tretinoin/administration & dosage ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Consolidation Chemotherapy ,Hematology ,medicine.disease ,3. Good health ,Leukemia ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Cytarabine ,business ,medicine.drug - Abstract
In standard-risk acute promyelocytic leukemia, recent results have shown that all-trans retinoic acid plus arsenic trioxide combinations are at least as effective as classical all-trans retinoic acid plus anthracycline-based chemotherapy while being less myelosuppressive. However, the role of frontline arsenic trioxide is less clear in higher-risk acute promyelocytic leukemia, and access to arsenic remains limited for front-line treatment of standard-risk acute promyelocytic leukemia in many countries. In this randomized trial, we compared arsenic, all-trans retinoic acid and the "classical" cytarabine for consolidation treatment (after all-trans retinoic acid and chemotherapy induction treatment) in standard-risk acute promyelocytic leukemia, and evaluated the addition of arsenic during consolidation in higher-risk disease. Patients with newly diagnosed acute promyelocytic leukemia with a white blood cell count 9 /L, after an induction treatment consisting of all-trans retinoic acid plus idarubicin and cytarabine, received consolidation chemotherapy with idarubicin and cytarabine, arsenic or all-trans retinoic acid. Patients with a white blood cell count >10x10 9 /L received consolidation chemotherapy with or without arsenic. Overall, 795 patients with acute promyelocytic leukemia were enrolled in this trial. Among those with standard-risk acute promyelocytic leukemia (n=581), the 5-year event-free survival rates from randomization were 88.7%, 95.7% and 85.4% in the cytarabine, arsenic and all-trans retinoic acid consolidation groups, respectively (P=0.0067), and the 5-year cumulative incidences of relapse were was 5.5%, 0% and 8.2%. (P=0.001). Among those with higher-risk acute promyelocytic leukemia (n=214), the 5-year event-free survival rates were 85.5% and 92.1% (P=0.38) in the chemotherapy and chemotherapy plus arsenic groups, respectively, and the corresponding 5-year cumulative incidences of relapse were 4.6% and 3.5% (P=0.99). Given the prolonged myelosuppression that occurred in the chemotherapy plus arsenic arm, a protocol amendment excluded cytarabine during consolidation cycles in the chemotherapy plus arsenic group, resulting in no increase in relapse. Our results therefore advocate systematic introduction of arsenic in the first-line treatment of acute promyelocytic leukemia, but probably not concomitantly with intensive chemotherapy, a situation in which we found myelosuppression to be significant. (ClinicalTrials.gov Identifier: NCT00378365).
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- 2018
45. Phase 3 results for vosaroxin/cytarabine in the subset of patients ≥60 years old with refractory/early relapsed acute myeloid leukemia
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Hamid Sayar, Heinz A. Horst, Stephen A. Strickland, Arnaud Pigneux, Gary J. Schiller, Michael Craig, Robert K. Stuart, Miklos Egyed, Renee Ward, Elias Jabbour, Jennifer A. Smith, Hagop M. Kantarjian, Jorge E. Cortes, Gary Acton, Utz Krug, Angelo Michele Carella, Farhad Ravandi, Ellen K. Ritchie, Judith A. Fox, Adam R. Craig, Norbert Vey, Jeffrey E. Lancet, Virginia M. Klimek, and Christian Recher
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Oncology ,medicine.medical_specialty ,Standard of care ,business.industry ,Myeloid leukemia ,Hematology ,Vosaroxin ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Refractory ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Cytarabine ,In patient ,Online Only Articles ,business ,030215 immunology ,medicine.drug - Abstract
Refractory/early relapsed (Ref/eRel) acute myeloid leukemia (AML) in patients ≥60 years old is the most important unmet medical need in the salvage setting, where outcomes are exceptionally poor and no standard of care exists.[1][1] Vosaroxin is a first-in-class anticancer quinolone derivative
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- 2018
46. Molecular Characteristics of Response to Olutasidenib (FT-2102) in Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia
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Sylvie Guichard, Andrew H. Wei, Brian A. Jonas, Jennifer Sweeney, Christophe Marzac, Justin M. Watts, Jürgen Krauter, A Khwaja, Pierre Peterlin, Joseph G. Jurcic, Carolyn S. Grove, Montserrat Arnan Sangerman, Daniela Cilloni, Jorge E. Cortes, Pau Montesinos, David Taussig, Karen W.L. Yee, Alex Sedkov, Antonio Curti, Jay Yang, Zihao Xin, Xavier Thomas, Devendra K Hiwase, Christian Recher, Jordi Esteve, Pierre Fenaux, Stéphane de Botton, Thorsten Braun, Arnaud Pigneux, William Blum, and Olivier Legrand
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Immunology ,Relapsed refractory ,medicine ,Myeloid leukemia ,In patient ,Cell Biology ,Hematology ,business ,Biochemistry - Abstract
Background: Olutasidenib is a potent, selective, oral, small molecule inhibitor of mutant IDH1 (mIDH1). Olutasidenib has previously shown clinical activity in high-risk AML patients (pts) in a Phase 1 clinical trial (Watts, Blood 2019). The planned interim analysis of an ongoing Phase 2 clinical trial (NCT02719574) in R/R mIDH1 AML pts receiving single-agent olutasidenib 150 mg twice-daily showed an overall response rate (ORR) of 46%, including 33% of pts with CR/CRh (de Botton et al., ASCO/EHA 2021). Here we present data analysis on the mutational characteristics of these pts and the relationship between mutations and clinical response. Methods: The Efficacy Evaluable (EE) set comprised mIDH1R132X pts whose first dose was ≥180 days before the data cut-off (18-JUN-20). The primary endpoint was CR/CRh (complete remission [CR] according to modified IWG 2003 criteria plus CR with partial hematologic recovery [CRh]) response rate. CRh was defined as bone marrow blasts 0.5×10 9/L, and platelet count >50×10 9/L. ORR, a secondary endpoint, comprised CR+CRh+CR with incomplete recovery (CRi) + morphologic leukemia-free state (MLFS) + partial remission (PR). IDH1 mutation subtypes were determined by central analysis, co-mutations were reported by investigators. Baseline characteristics and mutation subtypes were tabulated for the safety population and analysis of response rate by mutation type was performed on the EE set. Results: There were 153 R/R AML pts treated with olutasidenib 150 mg BID (safety set). Of those, 123 were in the efficacy evaluable (EE) set (centrally confirmed IDH1R132 mutation and received first dose at least 180 days prior to the data cut off). For the safety population, cytogenetic risk classification was favorable in 6 (4%) pts, intermediate in 109 (71%) pts, and poor in 25 (16%) pts (unknown, 13 [8%] pts). Eighty-five (56%) pts had IDH1R132C mutation subtype, followed by IDH1R132H (n=35 [23%]), IDH1R132G (n=12 [8%]), IDH1R132S (n=11 [7%]), and IDH1R132L (n=4 [3%]). Ninety-four (61%) pts had 1-3 co-mutations reported by the investigator at baseline, with 4-7 co-mutations in 20 (13%) pts, none in 6 (4%) pts, and not done/unknown in 33 (22%) pts. The most common co-mutations at baseline were: NPM1 (n=40 [26%]), DNMT3A (n=36 [24%]), and ASXL1 (n=21 [14%]. Receptor tyrosine kinase (RTK) mutations were reported in 32 (21%) pts (FLT3, n=18 [12%]; NRAS, n=10 [7%]; KRAS, n=3 [2%]; PTPN11, n=3 [2%]; KIT, n=2 [1%]; NF1, n=2 [1%]), with multiple mutations reported in some pts. For the EE population, responses were achieved in all IDH1R132 mutation subtypes, with ORR and CR/CRh response rates ranging from 27%-54% and 17%-50%, respectively (Table 1). The CR/CRh response rate was lower for pts with IDH1R132H mutations; notably, these pts tended to have a higher percentage of co-mutations, particularly mutations in NPM1 and RTK genes, including FLT3. For EE pts with available co-mutation data (n=96), the mean (SD) number of co-mutations was lower (p Conclusions: Responses were observed across IDH1R132 mutation subtypes, with a relatively lower CR/CRh response rate for pts with a R132H mutation as compared to other subtypes. Pts with a best response of CR/CRh had fewer co-mutations than pts who did not achieve CR/CRh. While the ORR was not significantly reduced for pts with RTK mutations, these pts had a lower CR/CRh response rate compared to pts without any RTK mutations. Additional genetic analyses using ddPCR for IDH1 mutations and NGS on a targeted panel of genes at baseline, best response, and end of study will be presented to further explore primary and secondary resistance mechanisms. Figure 1 Figure 1. Disclosures De Botton: Celgene, Agios, Forma Therapeutics, Astella, Daiichi Sankyo, Syros, Abbvie, Bayer, Seattle Genetics, Janssen: Honoraria; Celgene, Agios, Astellas, Daiichi Sankyo, Syros, Abbvie, Bayer, Janssen, Pierre Fabre, Novartis, Pfizer, Servier: Consultancy; Celgene: Speakers Bureau; Agios, Forma Therapeutics: Research Funding. Yee: Forma Therapeutics: Research Funding; Onconova: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MedImmune: Research Funding; Jazz: Research Funding; Tolero: Research Funding; AbbVie: Honoraria; F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Geron: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; TaiHo: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Paladin: Membership on an entity's Board of Directors or advisory committees; Otsuka: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding. Recher: BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; Janssen: Honoraria; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MaatPharma: Research Funding; Macrogenics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Wei: Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Macrogenics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Montesinos: Forma Therapeutics: Consultancy; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Tolero Pharmaceutical: Consultancy; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: 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, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Glycomimetics: Consultancy; Stemline/Menarini: Consultancy; Agios: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board, Research Funding, Speakers Bureau. Pigneux: Amgen: Consultancy; Sunesis: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Braun: Servier: Research Funding; Daiichi-Sankyo, Celgene: Consultancy, Honoraria. Curti: Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Esteve: Novartis: Consultancy, Research Funding; Jazz: Consultancy; Pfizer: Consultancy; Astellas: Consultancy; Novartis: Research Funding; Bristol Myers Squibb/Celgene: Consultancy; Abbvie: Consultancy. Grove: Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Jonas: 47, AbbVie, Accelerated Medical Diagnostics, Amgen, AROG, Celgene, Daiichi Sankyo, F. Hoffmann-La Roche, Forma, Genentech/Roche, Gilead, GlycoMimetics, Hanmi, Immune-Onc, Incyte, Jazz, Loxo Oncology, Pfizer, Pharmacyclics, Sigma Tau, Treadwell: Research Funding; AbbVie, BMS, Genentech, GlycoMimetics, Jazz, Pfizer, Takeda, Treadwell: Consultancy; AbbVie: Other: Travel reimbursement. Khwaja: Pfizer, Abbvie: Honoraria; Novartis, Jazz: Speakers Bureau. Blum: Forma Therapeutics, Xencor; Celyad: Research Funding; Amerisource Bergen; Abbvie, Syndax: Honoraria. Hiwase: Novartis: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Jurcic: AbbVie, BMS/Celgene, Novartis: Consultancy; AbbVie, Arog Pharmaceuticals, Astellas, BMS/Celgene, Forma Therapeutics, Genentech, Gilead Sciences, PTC Therapeutics, Syros Pharmaceuticals: Research Funding. Watts: Rafael Pharmaceuticals: Consultancy; Genentech: Consultancy; Bristol Myers Squibb: Consultancy; Takeda: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Aptevo Therapeutices: Research Funding. Xin: Forma Therapeutics, Inc.: Current Employment. Sedkov: Forma Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Guichard: Forma Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Sweeney: Forma Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Cortes: Sun Pharma: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Astellas, Novartis, Pfizer, Takeda, BioPath Holdings, Incyte: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Bio-Path Holdings, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding. Fenaux: Syros Pharmaceuticals: Honoraria; JAZZ: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding.
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- 2021
47. Prognostic Significance of DDX41 Germline Mutations in Intensively Treated AML Patients: An ALFA-Filo Study
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Laetitia Largeaud, Arnaud Pigneux, Eric Delabesse, Raphael Itzykson, Stéphane de Botton, Hervé Dombret, Juliette Lambert, Nicolas Duployez, Emmanuelle Clappier, Claude Preudhomme, Marie Sebert, Matthieu Duchmann, Christian Recher, Claude Gardin, Xavier Thomas, and Audrey Bidet
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Germline mutation ,business.industry ,Immunology ,Cancer research ,Medicine ,Cell Biology ,Hematology ,business ,Biochemistry - Abstract
Background: The WHO 2016 classification identifies myeloid malignancies with germline predisposition as a distinct subgroup (Arber DA et al., Blood 2016). We and other reported mutations of the DEAD-box RNA helicase 41 gene (g DDX41m) as the most common predisposition to MDS/AML (Sébert et al., Blood 2019). Relatively good outcomes have been suggested in small cohorts receiving heterogeneous treatment, but the prognostic significance of g DDX41m in AML patients (pts) treated with intensive chemotherapy (IC) has never been reported. Here, we analyzed the prognostic impact of g DDX41m in a large cohort of newly diagnosed AML pts treated with IC in 5 prospective ALFA (Acute Leukemia French Association) and FILO (French Innovative Leukemia Organization) trials. Methods: We retrospectively screened 1690 AML pts (aged 18-85y) treated in ALFA0701 (EudraCT 2007-002933-36), ALFA0702 (NCT00932412), ALFA1200 (NCT01966497), ALFA1401 (NCT02473146) and LAM-SA (NCT00590837) clinical trials for DDX41 mutations using High Throuput Sequencing. DDX41 variants with a variant allele frequency (VAF) >40% were interpreted as causal if they were pathogenic or likely pathogenic by the American College of Medical Genetics and Genomics (ACMG) guidelines. The concurrence of a somatic DDX41 mutation was also considered as a strong evidence for the causality. Correlation between g DDX41m and covariates was realized using point biserial correlation and Fisher test for continuous and dichotomic variables, respectively. Allogeneic hematopoietic stem cell transplantation (HSCT) was considered as a time-depending variable, and all outcome analyses were stratified on the clinical trial. Results: We identified 86 unrelated pts with DDX41-related AML representing 5% of the whole cohort; 66 (77%) of them had additional somatic DDX41 mutations. Most common germline variants were p.D140fs (21%), p.M1? (8%), p.L283fs (7%) and p.K331del (5%); p.R525H and p.G530D/C/S accounted for 80% and 10% of all somatic mutations respectively. Compared to wild-type pts, DDX41-related AML were significantly older (65.5 vs 64y, p=0.036), with male predominance (74 vs 54%, p=0.002), had higher rates of normal karyotypes (77 vs 57%, p=0.006), lower WBC (2.0 vs 7.9 G/L, p After one induction course, CR/CRp was achieved in 81 (94%) DDX41-related AML compared to 1164 (73%) in DDX41-wt pts. In a multivariate analysis including WBC, ELN-2017 classification and clinical trial, presence of a g DDX41m was associated with significant higher CR/CRp achievement (OR, 5.39 [95% CI, 2.33-15.67]; p=0.0004) (Figure 1B). After a median follow-up of 47.8 months, DDX41-related AML had a median OS of 39.7 (IQR, 19.4-66.4) months compared to 29.1 (IQR,10-not reached [NR]) months in DDX41wt (p=0.045). However, the prognostic impact on OS of g DDX41m was not independent of WBC and ELN-2017 classification (p=0.5). Relapse rates in DDX41-related pts were lower at 1-year (11 vs 30%), but then increased to join the relapse rates of DDX41-wt pts at 3 years (50 vs 50%, Figure 1C). Finally, 35 DDX41-related and 288 non-favorable DDX41-wt pts received an HSCT in first CR. HSCT was associated with a prolonged OS in the non-favorable DDX41-wt cohort (HR, 0.61 [95% CI, 0.49-0.76]; p Conclusion: This is the first study evaluating the prognostic impact of g DDX41m in a large cohort of AML pts prospectively treated with IC. DDX41-related AMLs represented a rare specific entity and were associated with a higher response rate, prolonged time to relapse without independent OS advantage compared to DDX41-wt AML. These results suggest that consolidation/maintenance strategy might be adapted in these pts. Figure 1 Figure 1. Disclosures Lambert: ASTELLAS: Consultancy; CELGENE/BMS: Consultancy. de Botton: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forma Therapeutics: Honoraria, Research Funding; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Syros: 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; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Other; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees. Recher: Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MaatPharma: Research Funding; Macrogenics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: 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, Research Funding; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Pigneux: Amgen: Consultancy; Sunesis: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Dombret: Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Novartis: Research Funding; Pfizer: Honoraria, Research Funding; Servier: Research Funding; Abbvie: Honoraria; BMS-Celgene: Honoraria; Daiichi Sankyo: Honoraria. Delabesse: Astellas: Consultancy; Novartis: Consultancy. Sebert: Abbvie: Consultancy; BMS: Consultancy.
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- 2021
48. Long-Term Outcome of Peripheral Blood Autologous Stem Cell Transplantation (AutoSCT) for De Novo Acute Myeloid Leukemia in Patients Achieving First Complete Remission after One Vs Two Induction Courses: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
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Norbert Claude Gorin, William Arcese, Silvia Maria Trisolini, Francesco Lanza, Myriam Labopin, Tobias Gedde-Dahl, Depei Wu, Anne Huynh, Gwendolyn Van Gorkom, Mohamad Mohty, Jacques-Emmanuel Galimard, Arnaud Pigneux, Didier Blaise, Arnon Nagler, and Marie-Thérèse Rubio
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Oncology ,medicine.medical_specialty ,Acute leukemia ,Marrow transplantation ,business.industry ,Immunology ,De novo acute ,Complete remission ,Myeloid leukemia ,Cell Biology ,Hematology ,Biochemistry ,Peripheral blood ,Autologous stem-cell transplantation ,Internal medicine ,medicine ,In patient ,business - Abstract
Background: Achieving a first complete remission (CR1) is the primary goal in the treatment of AML and is an important prognostic factor for transplantation outcome in general and even more so for autologous transplantation (AutoSCT). However, there are no data for AutoSCT indicating whether the number of chemotherapy courses (1 vs 2) needed to achieve CR1 is of prognostic significance for transplantation outcome. Methods: Using the EBMT/ALWP registry, we compared transplantation outcomes of adult patients (pts) aged ≥18 years with de novo AML that underwent a peripheral blood AutoSCT in 2000-2019 in CR1 achieved following one vs two chemotherapy courses. The primary outcome was the Leukemia Free Survival (LFS). Multivariate analysis (MVA) adjusting for differences between the groups and knowns factors were performed using Cox's proportional- hazards regression model for outcomes. Results: 1825 pts were included: 1532 (84%) with one and 293 (16%) with two induction chemotherapies courses. Time from diagnosis to AutoSCT was 4.7 (3.9-5.8) vs 5.7 (4.7-7.1) months, respectively (p 90 was higher in pts receiving 1 vs 2 inductions, 71% and 58% of pts, respectively (p Day 30 neutrophil engraftment incidence was 96% and 96.5%. Five -year non-relapse mortality (NRM) was 6.2% vs 6.0% for pts achieving CR1 with 2 vs 1 chemotherapy courses, respectively, and did not differ significantly (HR=1.31 (95% CI: 0.81-2.10), p=0.27). Five -year relapse incidence (RI) was higher :67.2% vs 52.3%, (HR=1.46 (95% CI: 1.25-1.72), p Conclusions: The five -year RI was higher and transplantation outcomes significantly inferior in pts with AML undergoing AutoSCT but who received two lines of chemotherapy to achieve CR1. Such pts may benefit from additional novel therapies in the conditioning or post-AutoSCT or be considered for allogeneic transplantation in an attempt to reduce their high RI and improve outcomes. Figure 1 Figure 1. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Blaise: Jazz Pharmaceuticals: Honoraria. Huynh: Jazz Pharmaceuticals: Honoraria. Mohty: Takeda: Honoraria; Jazz: Honoraria, Research Funding; Astellas: Honoraria; Janssen: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Gilead: Honoraria; Pfizer: Honoraria; Adaptive Biotechnologies: Honoraria; Sanofi: Honoraria, Research Funding. Pigneux: Amgen: Consultancy; Sunesis: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.
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- 2021
49. Real Life Study on Allogeneic Hematopoietic Cell Transplantation Practice According to International Guidelines and Its Impact on Survival in Acute Myeloid Leukemia French Population
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Nathalie Contentin, Alain Monnereau, Nicole Raus, Jean-Baptiste Mear, Gaelle Guillerm, Charlotte Jubert, Xavier Troussard, Arnaud Pigneux, Mohamad Sobh, Jacques-Olivier Bay, Sylvie François, Stephanie Nguyen Quoc, Edouard Forcade, Edouard Cornet, Sébastien Orazio, Marc Maynadié, Sylvain Chantepie, Denis Caillot, Remy Dulery, Mohamad Mohty, Marie Robin, Anna Berceanu, Loic Abed, Mauricette Michallet, and Morgane Mounier
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Oncology ,medicine.medical_specialty ,education.field_of_study ,Hematopoietic cell ,business.industry ,Immunology ,Population ,Myeloid leukemia ,Cell Biology ,Hematology ,Biochemistry ,Transplantation ,Internal medicine ,Medicine ,business ,Life study ,education - Abstract
Introduction Allogeneic Hematopoietic Cell Transplantation (allo-HCT) has proved its efficiency in reducing Acute Myeloid Leukemia (AML) recurrence, although it was associated with high rates of complications especially in older patients. The worldwide number of allo-HCT has increased within 35 years, from 10.000 transplantations before 1985 to over a million in 2012. The decision to perform transplantation depends on the estimated risk-benefit ratio. High-risk prognostic factors include cytogenetics, age at diagnosis, presence of comorbidities and the response to treatment. By using combination of risk factors, international recommendations have been published to harmonize AML care and maximize the benefit of using allo-HCT. The principal aim of this study is to describe real life AML care management in all consecutive patients diagnosed and registered on 3 regional cancer registries in France, to analyze their outcome after different therapeutic strategies, following or not the international recommendations. Method This retrospective study included all AML patients diagnosed between January 2012 and December 2016 reported to the French population data-based of regional cancer registries specialized in hematological malignancies. Allo-HCT data were extracted from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) registry. Two groups of patients were defined according to the treatment received: i) group 1, patients who have received the best recommended care including allo-HCT considering HLA compatibility and best donor choice or best conventional treatment according to therapeutic guidelines based on individuals and clinical characteristics from The American Society for Blood and Marrow Transplantation guidance; ii) group 2, patients who received a treatment outside the recommendations. To study the impact of therapeutic decision on overall survival, a case-control study was performed using a one for one matching between group 1 and group 2. An exact matching on individual and disease characteristics (cytogenetic risk, Charlson score class, age group at diagnosis, subtype AML and response to treatment) allowed to pair-match patients following or not the international recommendations for therapeutic strategy. Net survival was estimated until five-year using non-parametric Pohar-Perme estimator (survival distribution compared using Grafféo test). Results A total of 1039 AML patients diagnosed from 2012 to 2016 were identified, 449 (43 %) received a curative treatment and 540 patients a non-curative treatment (hypomethylating agents, low dose of cytarabine or other palliative treatment, best supportive care combined to no effective treatment). Based on available clinical data, 430 patients were included in the study. Group 1 included 296 patients (68%), 167 males and 129 females with 54 receiving allo-HCT (32 geno-identical and 22 unrelated). Group 2 included 134 patients (31%), 72 males and 62 females with 94 receiving allo-HCT (14 geno-identical, 50 unrelated and 30 mismatched). In patients for whom allo-HCT represented the best option according to the recommendations (Figure B, n = 44), a very significant lower survival was observed in patients who did not receive allo-HCT when they were compared to patients who received allo-HCT, with a 5 year-overall survival probability of 7 % and 50 % respectively (p= 0.019). In patients for whom allo-HCT was not recommended (Figure A, n = 42), we did not observe any significant difference of survival between patients transplanted or not. Conclusion This analysis shows the importance of allo-HCT decision in AML patients, especially when following international guidelines. Although individual risks factors have been previously studied, our analysis sums up theses factors and allow to understand the importance of integrating allo-HCT in the therapeutic strategy of AML and to re-evaluate current practices and its impact on patient outcome. Figure 1 Figure 1. Disclosures Pigneux: Roche: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Amgen: Consultancy; Novartis: Consultancy, Research Funding. Forcade: Novartis: Other: travel grant. Mohty: Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Sanofi: Honoraria, Research Funding; Adaptive Biotechnologies: Honoraria. Dulery: Novartis: Honoraria; Takeda: Consultancy; Gilead: Other: Travel support and registration fees for scientific meetings .
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- 2021
50. Long-Term Survival after Intensive Chemotherapy or Hypomethylating Agents in AML Patients Aged 70 Years and Older: A Large Patient Data Set Study from Dataml, SAL and Pethema European Registries
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Christian Recher, Christoph Röllig, Carsten Müller-Tidow, Claudia D. Baldus, Pau Montesinos, Suzanne Tavitian, Emilie Bérard, Martin Bornhäuser, Uwe Platzbecker, Eduardo Rodríguez-Arbolí, Audrey Bidet, Cristina Gil, Hubert Serve, Pierre-Yves Dumas, Teresa Bernal, Sarah Bertoli, Michael Kramer, David Martínez-Cuadrón, Josefina Serrano, Arnaud Pigneux, Pilar Rodríguez Martínez, Adolfo de la Fuente, Juan-Miguel Bergua, and Eric Delabesse
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Pediatrics ,medicine.medical_specialty ,business.industry ,Immunology ,Long term survival ,medicine ,Cell Biology ,Hematology ,Intensive chemotherapy ,Patient data ,Set (psychology) ,business ,Biochemistry - Abstract
The outcome of AML patients (pts) ≥ 70 years is poor. Defining the best treatment option remains controversial especially when choosing between intensive chemotherapy (IC) and hypomethylating agents (HMAs). We set up a multicentric European database collecting data of AML pts ≥ 70 y. The primary objective was to compare overall survival in pts selected for IC or HMAs. Individual pt data were collected from 3 European AML registries (DATAML, SAL and PETHEMA). All pts ≥70 y newly diagnosed between 01/01/2007 and 06/30/2018 were included. Variables were age, sex, diagnosis date, AML status, WBC, BM blasts %, cytogenetic risk, NPM1, FLT3-ITD mutations, first-line therapy, response, allo-SCT in first complete remission (CR), date of relapse and/or death. First-line treatments included IC, a semi-intensive regimen (fludarabine, cytarabine, filgrastim), HMAs, low-dose cytarabine (LDAC) or supportive care (SC). 3 700 AML pts ≥ 70y were identified. Pts treated with semi-intensive chemotherapy (n=464), LDAC (n=127) or SC (n=837) were not included in this analysis. Thus, the study population included 1 199 IC pts and 1 073 HMA pts. The median follow-up was 49.5 months. In the HMA group, pts were older, had lower WBC count and BM blast %, and they more frequently had ECOG > 1, secondary AML (sAML) and adverse-risk cytogenetics (CG) compared to the IC group. NPM1 and FLT3-ITD mutations were more frequent in the IC group. IC regimens were daunorubicin-AraC (n=432, 36.0%), idarubicin-AraC (n=381, 31.8%) or ida-AraC-CCNU (n=214, 17.8%). AlloSCT was performed in 70 IC pts (5.8%) and only in 7 HMA pts (0.7%) (P CR/CRi was achieved in 673 (56.1%) and 211 (19.7%) pts in the IC and HMA groups (P 1, adverse-risk CG and WBC >30 giga/L were significantly associated with a lower response rate whereas NPM1 mutation was significantly associated with a higher response rate. HMA treatment was associated with a lower response rate than IC (OR, 0.25; 95%CI : 0.20-0.31 ; P Day-60 death occurred in 247 (20.6%) and 194 (18.1%) pts in the IC and HMA groups (P=0.129). MV analysis showed that age ≥ 75 years, ECOG > 1, adverse-risk CG and WBC > 30 giga/L were significantly associated with a higher d60 death rate. HMA treatment was associated with a lower d60 death rate than IC (OR, 0.69; 95%CI : 0.54-0.88 ; P=0.003). The median OS was 10.9 (95%CI: 9.7-11.6) and 9.2 months (95%CI: 8.3-10.2) in the IC and HMA groups. OS at 1, 3 and 5 y was 46.0 (95%CI: 43.0-48.9) vs. 40.6% (95%CI: 37.6-43.7), 20.8 (95%CI: 18.3-23.4) vs. 8.3% (95%CI: 6.5-10.4) and 12.4 (95%CI: 10.2-14.9) vs 2.8% (95%CI: 1.7-4.4) in the IC and HMA groups. In MV analysis, ECOG > 1, adverse-risk CG, WBC > 30 giga/liter and sAML were significantly associated with a poorer OS. The treatment effect on OS was time-dependent (Fig 1A). To account for the non-proportionality of risks, we used a Royston and Parmar model, which took into account the interactions between time and treatment effect and allowed graphical representation of the adjusted risk of death at all times during follow-up. This model showed that HMA pts had a significantly lower risk of death before 1.5 months of follow-up ; there was no significant difference between both groups between 1.5 and 4.0 months, and OS was significantly better with IC from 4.0 months of follow-up (Fig 1B). There was no significant interaction between treatment (HMAs vs. IC) and all confounding factors (in particular age, performance status or CG risk). We also used the propensity score method. A MV logistic regression model was generated to estimate for each pt a propensity score to receive HMAs or IC. The performance of the model was estimated with the c 2-Hosmer-Lemeshow statistic (P-value= 0.169) and the C-statistic (0.82, 95%CI: 0.81-0.84). The mean propensity score was 0.320 (±0.232) in IC (N=1199) and 0.642 (±0.234) in HMA (N=1073). Based on propensity score, 532 subjects with IC were matched with 532 subjects with HMAs. The mean propensity score was the same in IC and HMA (0.491 ± 0.219) in the matched sample. The results of HMAs vs. IC comparisons on response, early mortality and overall survival (Fig 1C-D) in this subgroup of propensity score-matched pts were similar to those of the MV analysis. With a fairly long median follow-up and a large number of pts, this study shows that IC remains the treatment strategy that offers better chances for prolonged survival compared with HMAs even in AML pts ≥ 70y. Figure 1 Figure 1. Disclosures Recher: Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Macrogenics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MaatPharma: Research Funding. Bertoli: Astellas: Consultancy; BMS Celgene: Consultancy; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy. Dumas: Daiichi-Sankyo: Consultancy; Astellas: Consultancy; BMS Celgene: Consultancy. Tavitian: Novartis: Consultancy. Platzbecker: AbbVie: Honoraria; Geron: Honoraria; Celgene/BMS: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Janssen: Honoraria. Müller-Tidow: Janssen: Consultancy, Research Funding; Bioline: Research Funding; Pfizer: Research Funding. Baldus: Novartis: Honoraria; Amgen: Honoraria; Celgene/BMS: Honoraria; Jazz: Honoraria. de la Fuente: Incyte: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Novartis: Research Funding; BMS: Consultancy, Speakers Bureau. Delabesse: Novartis: Consultancy; Astellas: Consultancy. Pigneux: Roche: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Amgen: Consultancy; Novartis: Consultancy, Research Funding. Montesinos: Stemline/Menarini: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Glycomimetics: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Tolero Pharmaceutical: Consultancy; Forma Therapeutics: Consultancy; Agios: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board, Research Funding, Speakers Bureau.
- Published
- 2021
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