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1. Heterogeneity in long-term outcomes for patients with Revised International Staging System stage II, newly diagnosed multiple myeloma

Author

Anais Schavgoulidze, Valerie Lauwers-Cances, Aurore Perrot, Titouan Cazaubiel, Marie-Lorraine Chretien, Philippe Moreau, Thierry Facon, Xavier Leleu, Lionel Karlin, Anne-Marie Stoppa, Olivier Decaux, Karim Belhadj, Bertrand Arnulf, Mohamad Mohty, Clara M ariette, Cecile Fohrer-Sonntag, Pascal Lenain, Jean-Pierre Marolleau, Mourad Tiab, Carla Araujo, Frederique Orsini-Piocelle, Arnaud Jaccard, Murielle Roussel, Lotfi Benboubker, Jean-Richard Eveillard, Mamoun Dib, Marion Divoux, Michel Attal, Herve Avet-Loiseau, and Jill Corre

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

In the era of personalized treatment in multiple myeloma, high-risk patients must be accurately identified. The International Myeloma Working Group recommends using the Revised International Staging System (R-ISS) to pick out high-risk patients. The main purpose of our work was to explore the heterogeneity of outcome among R-ISS stage II patients assessing the impact of International Staging System (ISS) stage, chromosomal abnormalities and lactate dehydrogenase level in this subgroup. Data were collected from 1,343 patients up to 65 years old with newly diagnosed myeloma, enrolled in three clinical trials implemented by the Intergroupe Francophone du Myélome. All patients were eligible for intensive treatment. Patients in R-ISS stage II but ISS stage I had 1.6 times higher risk of death than patients in R-ISS stage I (adjusted hazard ratio=1.6; 95% confidence interval: 1.1-2.2; P=0.01) and patients in R-ISS stage II but with ISS stage III had a better overall survival than patients in R-ISS stage III (adjusted hazard ratio=0.7; 95% confidence interval: 0.4-0.9, P=0.02). However, among patients classified in R-ISS II, ISS stage and chromosomal abnormalities (del[17p] and t[4;14]) were still relevant prognostic factors for death. Dividing R-ISS stage II into three subgroups: ISS I with standard-risk chromosomal abnormalities, ISS II or III with standard-risk chromosomal abnormalities and patients with high-risk chromosomal abnormalities, median overall survival times were, respectively, not reached, 112 months and 71 months (P

Published
2022
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2. Heterogeneity in long term outcomes for R-ISS stage II in newly diagnosed multiple myeloma patients

Author

Anais, Schavgoulidze, Valerie, Lauwers-Cances, Aurore, Perrot, Titouan, Cazaubiel, Marie-Lorraine, Chretien, Philippe, Moreau, Thierry, Facon, Xavier, Leleu, Lionel, Karlin, Anne-Marie, Stoppa, Olivier, Decaux, Karim, Belhadj, Bertrand, Arnulf, Mohamad, Mohty, Clara M, Ariette, Cecile, Fohrer-Sonntag, Pascal, Lenain, Jean-Pierre, Marolleau, Mourad, Tiab, Carla, Araujo, Frederique, Orsini-Piocelle, Arnaud, Jaccard, Murielle, Roussel, Lotfi, Benboubker, Jean-Richard, Eveillard, Mamoun, Dib, Marion, Divoux, Michel, Attal, Herve, Avet-Loiseau, and Jill, Corre

Abstract

In the era of personalized treatment in multiple myeloma, high-risk patients must be accurately defined. The International Myeloma Working Group recommends using the Revised International Staging System (R-ISS) to identify high-risk patients. The main purpose of our work was to explore the heterogeneity of outcome among R-ISS stage II patients assessing the impact of ISS, chromosomal abnormalities (CA) and LDH level in this subgroup. Data were issued from 1,343 newly diagnosed myeloma patients up to 65 years, enrolled in 3 clinical trials implemented by the Intergroupe Francophone du Myelome. All patients were eligible to an intensive treatment. Patients R-ISS stage II but ISS stage I had 1.6 times more risk of death than patients R-ISS stage I (adjusted HR 1.6; 95% CI, 1.1 to 2.2; P = .01) and patients R-ISS stage II but ISS stage III had a better overall survival than patients R-ISS stage III (adjusted HR 0.7; 95% CI, 0.4 to 0.9, P = .02). However, among patients classified in R-ISS II, ISS stage and CA (del(17p) and t(4;14)) were still relevant prognostic factors for death. Dividing R-ISS stage II into 3 subgroups: ISS I with standard risk CA, ISS II or III with standard risk CA and, high risk CA patients, median overall survivals were respectively not reached, 112 and 71 months (P0.001). In conclusion, stratification of patients in the R-ISS stage II group can be improved by taking into account CA and ISS. However, this does not improve predictive performance of survival models.

Published
2021

3. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma

Author

Philippe Moreau, Laurent Garderet, Bertrand Arnulf, Sabrina Maheo, Lotfi Benboubker, Mamoun Dib, Sabine Brechignac, Nelly Robillard, Mohamad Mohty, Margaret Macro, Brigitte Pegourie, Thierry Facon, Brigitte Kolb, Karim Belhadj, Nikhil C. Munshi, Bruno Royer, Olivier Decaux, Arnaud Jaccard, Valérie Lauwers-Cances, Marie-Lorraine Chretien, Anne-Marie Stoppa, Hervé Avet-Loiseau, Xavier Leleu, Kenneth C. Anderson, Jean-Richard Eveillard, Martin Moorhead, Chantal Doyen, Cecile Fohrer, Lionel Karlin, Jill Corre, Victoria Carlton, Paul G. Richardson, Malek Faham, Jean-Luc Harousseau, Michel Attal, Nathalie Meuleman, Thomas D. Willis, Aurore Perrot, Cyrille Hulin, Thomas Dejoie, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'épidémiologie [Toulouse], CHU Toulouse [Toulouse], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Service d'Hématologie Biologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Biochimie [Nantes], Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Universitaire [Grenoble] (CHU), 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'hématologie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d’Hématologie Clinique [Rennes], CHU Pontchaillou [Rennes], Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Universitaire de Bobigny, Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hôpital Universitaire de Caen, Department of Energy / Joint Genome Institute (DOE), Los Alamos National Laboratory (LANL), Département d'Hématologie Clinique [CHU Nantes], Département d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département d'Hématologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département d'Hématologie [CHU Nantes], 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Hématologie [IUCT Oncopole, Toulouse], Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Département d'hématologie [CHU Saint-Antoine, AP-HP], AP-HP - Hôpital Saint-Antoine, Institut Jules Bordet, Service hématologie (CHU d'Amiens), Département d'Hématologie Clinique [CHU Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, 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), and Service d'Hématologie [CHU Toulouse]

Subjects
Male, 0301 basic medicine, Oncology, Neoplasm, Residual, Biochemistry, Dexamethasone, Bortezomib, Observations Lymphoid Neoplasia, 0302 clinical medicine, Maintenance therapy, Bone Marrow, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Lenalidomide, Multiple myeloma, Lymphoid Neoplasia, Hazard ratio, High-Throughput Nucleotide Sequencing, Hematology, Minimal Residual Disease Negativity, Middle Aged, Prognosis, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, medicine.drug, medicine.medical_specialty, Plasma Cells, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, Internal medicine, medicine, Humans, Clinical Trials, Survival rate, Aged, business.industry, Cell Biology, medicine.disease, Minimal residual disease, Transplantation, 030104 developmental biology, business, Follow-Up Studies
Abstract

IF 15.132 (2017); International audience; The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (

Published
2018
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4. FDG PET to Diagnose Neurolymphomatosis in a Case of Triple-Hit B-Cell Lymphoma

Author

Philippe Trensz, C. Heimburger, Izzie Jacques Namer, Caroline Bund, Stéphane Kremer, and Cecile Fohrer

Subjects
Male, medicine.medical_specialty, Lymphoma, B-Cell, Nerve root, Medullary cavity, medicine.medical_treatment, Spinal mri, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Marek Disease, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, B-cell lymphoma, Neoplasm Staging, Chemotherapy, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Lymphoma, 030220 oncology & carcinogenesis, Radiology, business
Abstract

A 46-year-old man with stage IV triple-hit B-cell lymphoma diagnosed in February 2016 was treated with chemotherapy. He was followed classically with FDG PET/CT, which assessed the complete metabolic response in June 2016. In July 2016, he had autologous stem cell transplantation. Two months later, he underwent an FDG PET/CT for revaluation. It showed intense FDG uptake in the medullary canal from cervical 4 to thoracic 4, bilateral cervical 7 to thoracic 8, and right thoracic 9 to 12 nerve roots, leading to the diagnosis of neurolymphomatosis. A clinical cervical radiculopathy and spinal MRI results reinforced this diagnosis.

Published
2017
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5. Heavy + light chain analysis to assign myeloma response is analogous to the IMWG response criteria

Author

Benjamin Hebraud, Philippe Moreau, Loïc Renaud, Bertrand Arnulf, Brigitte Kolb, Lionel Karlin, Margaret Macro, Cyrille Hulin, Deborah Desmier, Bruno Royer, Brigitte Pegourie, Aurore Perrot, Cecile Fohrer, Antoine Machet, Denis Caillot, Guillemette Fouquet, Xavier Leleu, Hervé Avet-Loiseau, Eileen M Boyle, Thomas Systchenko, Thomas Dejoie, Thierry Facon, Valentine Richez, Olivier Decaux, Cécile Gruchet, Susanna Schraen, Stephen Harding, Kym I E Snell, Niels Moya, Stéphanie Guidez, Hôpital Claude Huriez [Lille], CHU Lille, University of Birmingham [Birmingham], CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de biologie pathologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de Hautepierre [Strasbourg], Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], hôpital Sud-Rennes, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Universitaire de Caen, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Amiens-Picardie, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôtel-Dieu de Nantes, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Poitiers-CHU de Poitiers-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU de Poitiers, Hôpital de la Côte de Nacre, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Universitaire du Cancer de Toulouse - Oncopole ( IUCT Oncopole - UMR 1037 ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), Centre Hospitalier Universitaire [Grenoble] ( CHU ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), and Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy )

Subjects
Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, response evaluation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunoglobulin light chain, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Cohen's kappa, Monitoring, Immunologic, Multiple myeloma, Internal medicine, Biomarkers, Tumor, medicine, Overall survival, Humans, Response criteria, Aged, Aged, 80 and over, Immunoassay, business.industry, Remission Induction, Hematology, Middle Aged, Prognosis, medicine.disease, 3. Good health, Survival Rate, 030104 developmental biology, Immunology, Female, Immunoglobulin Light Chains, Immunoglobulin Heavy Chains, business, heavy + light chain, Follow-Up Studies
Abstract

IF 2.755; International audience; Automated serum heavy + light chain (HLC) immunoassays can measure the intact immunoglobulins of each light chain type separately. We though to compare HLC assays with electrophoretic techniques in determining International Myeloma Working Group (IMWG) response criteria. 114 myeloma patients from 2 trials were included. HLC measurements were made utilizing archived sera and response assessments compared with those based on electrophoretic analysis at the time of the trials. Assessments at ∼90 days and maximal response were compared as was the power of the 2 techniques for predicting later responses, overall survival, and progression. The kappa statistic indicated good agreement between the 2 methods for determining IMWG response criteria, although HLC measurements might give better predictions of subsequent responses and frequently gave an earlier indication of change. HLC measurements could represent an alternative to electrophoretic techniques in determining IMWG response. Validation with a greater range of patient responses is needed for confirmation.

Published
2017
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6. Le lymphome du système nerveux central, un grand simulateur

Author

Cécilia Alves Do Rego, Thomas Wirth, Laurent Kremer, Stéphane Kremer, Elise Toussaint, Jérôme De Seze, and Cecile Fohrer

Subjects
Neurology, Neurology (clinical)
Abstract

Introduction Le lymphome du systeme nerveux central (LSNC) est une tumeur rare pouvant mimer d’autres pathologies du SNC. Nous rapportons 3 cas de lymphomes cerebraux et discutons les difficultes diagnostiques rencontrees. Observation Cas 1 : patient de 58 ans adresse pour paraparesie et troubles vesicosphincteriens. L’IRM lombaire notait une lesion d’allure tumorale de la queue de cheval, la ponction lombaire (PL) une meningite lymphocytaire normoglycorachique. Deux cures de solumedrol permirent de faire regresser la lesion. Quatre ans plus tard apparut une lesion frontale gauche responsable de troubles du comportement. La biopsie objectiva un lymphome B diffus a grandes cellules (LBDGC). Cas 2 : patiente de 61 ans aux antecedents de LBDGC sans atteinte du SNC, se presentant pour une atteinte du VII et du VIII gauche associee a une hemiparesie droite. L’IRM cerebrale notait une lesion frontoparietale gauche en restriction en ADC evoquant un possible infarctus cerebral, la PL etait normale. Le PET scan retrouvait un hypermetabolisme de la lesion orientant le diagnostic vers une recidive cerebrale du lymphome. Cas 3 : patiente de 52 ans se presentant pour une atteinte multiple des nerfs crâniens avec une meningite lymphocytaire hypoglycorachique et une prise de contraste meningee limitee au pont. Apres absence de reponse a un traitement antituberculeux, la biopsie du nerf trijumeau conclut a un LBDGC. Discussion Les caracteristiques cliniques et IRM du LSNC sont extremement polymorphes comme l’ont soulignees les observations precedentes. Le LSNC peut ainsi mimer aisement un infarctus cerebral, une meningite bacterienne chronique ou des lesions pseudotumorales de sclerose en plaque. Parfois seul l’anatomopathologie permet de redresser le diagnostic et d’initier une chimiotherapie efficace. Conclusion Le lymphome cerebral du systeme nerveux central doit etre evoque devant une lesion cerebrale atypique d’apparition aigue ou subaigue. Le recours a la biopsie cerebrale doit etre realise avant l’introduction des corticoides.

Published
2018
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7. Le pomalidomide dans le myélome multiple

Author

Xavier Leleu, Luc Renaud, Stéphanie Guidez, Lionel Karlin, Cecile Fohrer, Bertrand Arnulf, Charles Herbaux, Guillemette Fouquet, M. Macro, Hélène Demarquette, Lotfi Benboubker, C Prod'homme, M. Roussel, Olivier Decaux, C. Hulin, C. Le Grand, Claire Bories, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Drug, Oncology, medicine.medical_specialty, ésMyélome multiple, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Immunomodulation, 03 medical and health sciences, 0302 clinical medicine, Refractory, Internal medicine, Internal Medicine, medicine, IMiD, Multiple myeloma, 030304 developmental biology, media_common, Lenalidomide, 0303 health sciences, [ SDV ] Life Sciences [q-bio], Bortezomib, business.industry, Disease progression, Gastroenterology, Pomalidomide, medicine.disease, 3. Good health, Thalidomide, 030220 oncology & carcinogenesis, business, Multiple Myeloma, medicine.drug
Abstract

National audience; Résumé Auparavant caractérisé par un très mauvais pronostic, le myélome multiple (MM) est aujourd’hui compatible avec une survie prolongée, grâce aux progrès majeurs liés à l’utilisation des « nouveaux agents » : les inhibiteurs du protéasome (dont le bortézomib) et les IMiD (immunomodulateurs, tels que la thalidomide ou le lénalidomide). Cependant, la grande majorité des patients – si ce n’est tous les patients – vont rechuter et devenir éventuellement réfractaires à tous les traitements disponibles, y compris ces nouveaux agents. Il reste donc des progrès à faire dans cette situation, notamment via le développement de la prochaine génération d’inhibiteurs du protéasome et d’IMiD, et le développement de nouvelles classes thérapeutiques. Cette revue se concentre sur le pomalidomide, un IMiD de nouvelle génération dont l’utilisation a été récemment approuvée par la Food and Drug Administration (FDA) aux États-Unis et l’European Medicines Agency (EMA) en Europe, pour les patients présentant un myélome multiple en rechute ou réfractaire, ayant déjà reçu au moins 2 lignes thérapeutiques dont le lénalidomide et le bortézomib, et dont la maladie a progressé au cours de leur dernière ligne de traitement. Abstract Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of “novel agents”: proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority – if not all – of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This review focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy

Published
2015
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8. Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients

Author

Benjamin Hebraud, Cecile Fohrer, M. Attal, Valérie Lauwers-Cances, François Guilhot, Jill Corre, T. Lamy, Lionel Karlin, Hervé Avet-Loiseau, Laurent Garderet, Murielle Roussel, Catherine Sebban, C Gentil, Thierry Facon, Christophe Fruchart, Denis Caillot, Frédérique Orsini-Piocelle, Mamoun Dib, Jean Fontan, Jérôme Jaubert, Stoppa Am, Brigitte Pegourie, Gérard Lepeu, Philippe Moreau, Xavier Leleu, Claudine Sohn, C. Hulin, Gerald Marit, Sabine Brechignac, and Margaret Macro

Subjects
Oncology, Male, Cancer Research, Prognostic factor, medicine.medical_specialty, Pathology, Multivariate analysis, Article, Cohort Studies, Internal medicine, Medicine, Humans, Multiple myeloma, In Situ Hybridization, Fluorescence, Univariate analysis, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Hematology, medicine.disease, Prognosis, Chromosomes, Human, Pair 1, Homogeneous group, Female, Chromosome Deletion, business, Multiple Myeloma, Cohort study, Fluorescence in situ hybridization
Abstract

Deletions of the 1p region appear as a pejorative prognostic factor in multiple myeloma patients (especially 1p22 and 1p32 deletions) but there is a lack of data on the real impact of 1p abnormalities on an important and homogeneous group of patients. To address this issue we studied by fluorescence in situ hybridization (FISH) the incidence and prognostic impact of 1p22 and 1p32 deletions in 1195 patients from the IFM (Institut Francophone du Myelome) cell collection. Chromosome 1p deletions were present in 23.3% of the patients (271): 15.1% (176) for 1p22 and 7.3% (85) for 1p32 regions. In univariate analyses, 1p22 and 1p32 appeared as negative prognostic factors for progression-free survival (PFS): 1p22: 19.8 months vs 33.6 months (P

Published
2013

9. Trastuzumab (Herceptin®) for Treatment of Refractory/Relapsed HER2 Positive Adult B-ALL: Results of a Phase II GRAALL Study

Author

Patrice Chevallier, Nelly Robillard, Aude Charbonnier, Emmanuel Raffoux, Sébastien Maury, Sylvain Carras, Cecile Chabrot, Cecile Fohrer, Marc Bernard, Jean-Sebastien Blade, Anne Etienne, Pascaline Talmant, Jacques Delaunay, Thierry Guillaume, Mohamad Mohty, Norbert Ifrah, and Herve Dombret

Subjects
Immunology, Cell Biology, Hematology, skin and connective tissue diseases, Biochemistry
Abstract

Abstract 1525 Trastuzumab (rhu-mAb-HER2, Herceptin®, F. Hoffmann-La Roche, Basel, Switzerland) is the humanized equivalent of the murine 4D5 monoclonal antibody targeted against the HER2 cell-surface receptor. In combination with chemotherapy, trastuzumab has significantly improved the outcome of women with HER2+ breast cancer. We have previously shown that HER2 surface antigen is up-regulated in around one third of adult B-ALL and is associated with chemoresistance in these patients (Chevallier et al, Haematologica, 2004). We report here for the first time the results of a Phase II study evaluating the safety and efficacy of trastuzumab in refractory/relapsed HER2 + adult B-ALL patients. Prior to patient inclusion, HER2 positivity was assessed using multicolor flow cytometry with the phycoerythrin-conjugated HER2 Neu 24.7 antibody (BD) and a CD19+ CD45+low blast cell gating strategy. The mean fluorescence intensity (MFI) ratio was obtained by dividing the MFI of HER2 with that of its isotypic control. HER2 positivity threshold was defined by a ratio intensity (RI) >= 2. Also, HER2 oncogene amplification was assessed by FISH analysis using the HER2 DNA probe kit (Vysis, Downers Grove, IL, USA). Relapsed/refractory B-ALL patients aged >=18 years and with a HER2+ expression for at least 30% of the leukemic blast population in peripheral blood (PB) and/or bone marrow (BM) were included. Left ventricular ejection fraction has to be > 50%. All patients gave informed consent and the protocol was approved by the required regulatory authorities. The trial was registered at http://clinicaltrials.gov/ct no.NCT00724360. Trastuzumab was administered according to the approved schedule in breast cancer patients at 4 mg/kg intravenous loading dose followed by 2 mg/kg weekly. There was no corticosteroid premedication. Trastuzumab was provided by Roche. Out of 50 patients screened for the HER2 expression, 15 patients (30%) (male n=8; female n=7), with a median age of 62 years (range: 24–80), have been included in the study between November 2006 and July 2011. This was considered as a very high-risk population: 2 patients had refractory disease after 2 induction courses, 2 patients were in first untreated relapse while 11 patients had a refractory first relapse or were beyond first relapse. Median percentage of HER2+ leukemic blast population was 94% (range: 0–100) in PB and 100% (range: 31–100) in BM. Surprisingly, no HER2 gene amplification was detected in samples assayed by FISH. Normal and complex karyotype were detected in 7 and 3 patients respectively. Three patients had a Phi+ B-ALL, and 1 patient a monosomy 7 (unknown karyotype n=1). Currently, 3 patients are still receiving therapy. Considering the 12 other patients, the median number of trastuzumab infusions was 4 (1 month of treatment) (range: 2–20). No grade 3–4 toxicities were observed, with no cardiotoxic events. The overall response rate (CR or PR (decrease >=50% of blast population) or blast clearance in BM or PB) was 33%. No CR was observed. Two patients achieved partial response in BM (92% vs 12% after 9 infusions with loss of HER2 expression on blast population, total number of infusions (TNI) n=18); 25% vs 11% after 4 injections, TNI n=13) while blast clearance was observed in 2 other patients (96% vs 57% of blasts in BM after 8 infusions with loss of HER2 blast expression, TNI n=20; 20.5% vs 2% of blasts in PB after 3 infusions, TNI n=3). In all, we conclude that trastuzumab in monotherapy can allow for some responses in this very high-risk refractory/relapsed HER2+ adult B-ALL population. Combination of trastuzumab with chemotherapy or other therapeutic monoclonal antibodies should be tested in the future. An updated follow-up of the study will be provided during the meeting. Disclosures: No relevant conflicts of interest to declare.

Published
2011
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10. A systematic review of dimensions evaluating patient experience in chronic illness

Author

Bastien Forestier, Emmanuelle Anthoine, Ziad Reguiai, Cécile Fohrer, and Myriam Blanchin

Subjects
Chronic illness, Patient reported outcome measures, Patient reported experience measures, Patient-centered care, Patient experience, Systematic review, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background Living with a chronic disease often means experiencing chronic treatments and regular multidisciplinary monitoring as well as a profound life-changing experience which may impact all aspects of a patients life. The patient experience of chronic disease is frequently assessed by patient reported measures (PRMs) which incorporate patients perspectives to better understand how illness, treatment and care impact the entirety of a patient’s life. The purpose of this review was to collect and review different kinds of available PRM instruments validated for chronic patients, to produce an inventory of explored concepts in these questionnaires and to identify and classify all dimensions assessing chronic patients experience. Methods A systematic review of PRM instruments validated for chronic patients was conducted from three databases (Medline, the Cochrane library, and Psycinfo). Articles were selected after a double reading and questionnaires were classified according to their targeted concept. Then, all dimensions of the questionnaires were clustered into different categories. Results 107 primary validation studies of PRM questionnaires were selected. Five kinds of instruments were recorded: 1) Questionnaires assessing health related quality of life or quality of life; 2) Instruments focusing on symptoms and functional status; 3) Instruments exploring patients’ feelings and attitude about illness; 4) Questionnaires related to patients’ experience of treatment or healthcare; 5) Instruments assessing patients attitudes about treatment or healthcare. Twelve categories of dimensions were obtained from these instruments. Conclusions This review provided an overview of some of the dimensions used to explore chronic patient experience. A large PRM diversity exists and none of the reviewed and selected questionnaires covered all identified categories of dimensions of patient experience of chronic disease. Furthermore, the definition of explored concepts varies widely among researchers and complex concepts often lack a clear definition in the reviewed articles. Before attempting to measure chronic patient experience, researchers should construct appropriate instruments focusing on well-defined concepts and dimensions encompassing patient’s personal experience, attitude and adaptation to illness, treatment or healthcare.

Published
2019
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11. Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature

Author

Anne Sophie Weingertner, Marc Wilt, Ihab Atallah, Cécile Fohrer, Laurent Mauvieux, and Jean-François Rodier

Subjects
Acute myeloid leukaemia, Myeloid sarcoma of the uterine cervix, Radioiodine therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi 131I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of 131I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind.

Published
2009
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