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1. Comparative study of changes in maternal and perinatal morbidity inequalities among migrant and native women over time, between 2008 and 2014 in France

Author: Elie Azria, Michel Dreyfus, Maxime Eslier, Rémy Morello, Department of Obstetrics and Gynaecology, Hôpital Universitaire de Caen, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Gynécologie-Obstétrique et Médecine de la Reproduction [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)
Subjects: medicine.medical_specialty, Inequality, media_common.quotation_subject, Maternal morbidity, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Migrant women, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Perinatal morbidity, Humans, Medicine, 030212 general & internal medicine, Africa South of the Sahara, Retrospective Studies, media_common, Transients and Migrants, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics, Significant difference, Parturition, Obstetrics and Gynecology, medicine.disease, University hospital, 3. Good health, Gestational diabetes, Increased risk, Reproductive Medicine, Female, France, business
Abstract: Background An increased risk of severe maternal morbidity and mortality has been described in migrant women, particularly in those born in sub-Saharan Africa. The mechanisms in question are poorly identified and rarely studied specifically. Objective To compare changes in maternal and perinatal morbidity inequalities among migrant and native women over time, between 2008 and 2014. Material and method A retrospective, single-centre study carried out at the Maternity Unit of the University of Caen Hospital in France. All women who gave birth in 2008 or 2014 were included. Twin pregnancies and delivery before reaching 22 weeks of pregnancy were excluded. Pre-pregnancy characteristics and maternal and perinatal morbidities were collected from the university hospital’s medical and administrative database. We compared the maternal and perinatal morbidity in 2008 and 2014 of women born in France to the morbidity of women born abroad. Secondly, we compared these migrant women between 2008 and 2014 to see if changes in the characteristics of migrant women were associated with a change in the type of maternal and perinatal complications. Results Of the 3,038 and 3,001 women included in 2008 and 2014, respectively, 272 (9.0 %) and 385 (12.8 %) women were migrants. Compared to women born in France, we found two times more severe postpartum hemorrhages in women born in sub-Saharan Africa (aOR = 2.1[1.1−3.9]) and a significant increase in the risk of gestational diabetes in women born in North Africa (aOR = 1.9[1.2−2.9]). We found a significant increase in the risk of severe postpartum hemorrhage (aOR = 2.1[1.5−3.0]) and gestational diabetes (aOR = 3.0[2.5−3.7]) in 2014 compared to 2008. We did not find a significant difference in perinatal morbidity between 2008 and 2014. Conclusion We noted a significant increase in the risk of severe postpartum hemorrhage in women born in sub-Saharan Africa and gestational diabetes in women born in North Africa compared to those born in France, and these risks increase in 2014 relative to 2008.
Published: 2020
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2. 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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3. Comparative study between women born in France and migrant women with regard to their mode of delivery

Author: Maxime Eslier, Rémy Morello, Elie Azria, Michel Dreyfus, Department of Obstetrics and Gynaecology, Hôpital Universitaire de Caen, Unité de Biostatistique et de Recherche Clinique (UBRC), 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), Normandie Université (NU), Maternity Unit, Paris Saint Joseph Hospital, DHU Risks in Pregnancy, Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-DHU Risks in Pregnancy, Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5), 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 (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Adult, medicine.medical_specialty, Migrants, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Humans, Retrospective Studies, Transients and Migrants, 030219 obstetrics & reproductive medicine, Obstetrics, business.industry, Cesarean Section, Pregnant women, Obstetrics and Gynecology, Gestational age, Odds ratio, University hospital, medicine.disease, Delivery, Obstetric, Mode of delivery, Reproductive Medicine, 030220 oncology & carcinogenesis, Computer database, Observational study, Female, France, business
Abstract: Objective: To compare the mode of delivery between women born in France and migrants.Study design: The study was a retrospective, observational, single-center study conducted at the university maternity unit in Caen. All women who gave birth in 2008 or 2014 were included. Women with multiple pregnancies and women whose pregnancies ended before 22 weeks of gestational age were excluded. The pre-existing characteristics at the time of pregnancy, mode of delivery and postpartum were collected from the University Hospital's medical and administrative computer database. We first compared women born in France to those born abroad with regard to the characteristics of mode of delivery for 2008, then for 2014. Secondly, we compared migrant women between 2008 and 2014 to see if the change in the migration profile was associated with a change in the mode of delivery.Results: Of the 3038 and 3001 women included in 2008 and 2014 respectively, 272 and 385 women were migrants. We observed a significant decrease in the number of spontaneous labors (adjusted odds ratio (aOR) 0.5 [0.4-0.6]) with a significant increase in emergency cesarean sections before (aOR 2.1 [1.4-3.0]) and during labor (aOR 2.2 [1.6-3.2]) among women born in sub-Saharan Africa compared to nonmigrants. And we showed a higher risk of cesarean section prior to labor (aOR 1.2 [1.01-1.4]) and a significant decrease in cesarean section during labor (aOR 0.8 [0.7-0.99]) in 2014 compared to 2008.Conclusion: We observed a significant increase in all types of Cesarean sections among women born abroad compared to those born in France, especially in the subgroup of women born in sub-Saharan Africa. (C) 2019 Elsevier Masson SAS. All rights reserved.
Published: 2020
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4. Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

Author: Bertrand Joly, Hagay Sobol, Isabelle Azais, Hervé Avet-Loiseau, Karine Augeul-Meunier, Catherine Le Bris, Delphine Demangel, Maroulio Pertesi, Xavier Leleu, Maria Victoria Revuelta, Maxime Vallée, Manuel Cliquennois, James D. McKay, Aurore Perrot, Aleksandra Butrym, Matthieu Foll, Björn Nilsson, Javier Oliver, Judit Várkonyi, Emeline Perrial, Xiaomu Wei, Artur Jurczyszyn, Gabriele Buda, Marcin Rymko, Cécile Leyronnas, Robert J. Klein, Elżbieta Iskierka-Jażdżewska, Claire Mathiot, Marzena Wątek, Eric Voog, Olivier Decaux, Florence Desquesnes, Jill Corre, Arnon Nagler, Jean Gabriel Fuzibet, Véronique Dorvaux, Jan Maciej Zaucha, Philippe Rodon, Siwei Chen, Denis Caillot, Laurent Garderet, Michel Maigre, Isabelle Leduc, Fabienne Lesueur, Borhane Slama, Sophie Rigaudeau, Philippe Mineur, Norbert Grząśko, Perrine Galia, Rui Manuel Reis, Federico Canzian, Philippe Helias, Yves-Jean Bignon, Marcin Kruszewski, Victor Moreno, Juan Sainz, Nathalie Cheron, Laurent Voillat, Charles Dumontet, Christian Berthou, Marie Beaumont, Brigitte Pegourie, Etienne Paubelle, Marguerite Vignon, Matteo Pelosini, Philippe Casassus, Isabelle Lambrecht, Laure Vincent, Eileen M Boyle, Annette Juul Vangsted, Pascal Bourquard, Laurent Mosser, Margaret Macro, Gerald Marit, Daniele Campa, Brigitte Kolb, Bruno Royer, Jean Fontan, Ramón García-Sanz, Philippe Moreau, Serge Leyvraz, Malgorzata Krawczyk-Kulis, Krzysztof Jamroziak, Joaquin Martinez-Lopez, Bruno Anglaret, Steven M. Lipkin, Nicole Frenkiel, Ofure Obazee, Marek Dudziński, Pascale Cony-Makhoul, Hervé Naman, Andres Jerez, Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Genetic Cancer Susceptibility, Department of Biological Statistics and Computational Biology, Cornell University, Weill Medical College of Cornell University Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University [New York], Hospices Civils de Lyon (HCL), ProfileXpert, Université de Lyon, LCMT, ProfileXpert, Biomedical Research Institute of Málaga (IBIMA), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), CHU Saint-Antoine [APHP]-Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [APHP], Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7371, INSERM UMR S1146, Laboratoire d'Imagerie Biomédicale, France, parent, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Médecine Interne [CHU Rennes], Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hopital de Périgueux (CH Périgueux), Hopital de Périgueux, Service d'Hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Henri Duffaut (Avignon), Département Oncologie-Hématologie [Charleroi, Belgium], Grand Hôpital de Charleroi [Belgium], Centre Jean Bernard [Le Mans] (Institut Inter-Régional de Cancérologie), CHU de Fort de France (Service Post-Urgences, Pôle RASSUR), CHU de Fort de France, Hôpital JeanMinjoz, Centre hospitalier de Chartres (Chartres) (Service d'Hémato-Oncologie), Service hématologie (CHU d'Amiens), CHU Amiens-Picardie, Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [AP-HP Hôpital Saint-Louis], AP-HP Hôpital Saint-Louis, Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], CHU Saint Louis [APHP], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Médecine Interne [CHU Nice] (Hôpital l'Archet), Hôpital l'Archet-Centre Hospitalier Universitaire de Nice (CHU de Nice), Service d'hématologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier de Valence (Unité d'Hématologie), Centre hospitalier de Valence, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hematology Department - Namur Thrombosis and Hemostasis Center (NTHC), UCL Mont-Godinne, Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CHUV, Lausanne (Departement d'Oncologie), Unité d'Oncologie Médicale, Rodez (Hôpital Jacques Puel, Pôle Medical 2), Unité de coordination en oncogériatrie de Basse-Normandie [Caen] (UCOG Basse-Normandie), CHI Poissy-Saint-Germain, Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, CHG Abbeville (Hématologie), Institut Daniel Hollard [Grenoble], Service d'hématologie et oncologie [Centre Hospitalier de Chalon-sur-Saône William Morey], Centre Hospitalier Chalon-sur-Saône William Morey, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Intergroupe francophone du myélome (IFM), Service d'Onco-Hématologie, Centre Médical de Bligny, Briis sous Forges, Service Hématologie, CH LYON SUD, Pierre benite, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital Sud-Fancilien, CH Sud-Fancilien, Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU de Nîmes), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hématologie, Oncologie Médicale, Centre Azureen de cancérologie, Centre Azureen de cancérologie, Unité d'hématologie et d'oncologie [Centre Hospitalier de Versailles], Centre Hospitalier de Versailles (CHV), Inserm U1035, Biotherapies des Maladies Genetiques et Cancers, Univ Bordeaux, CHU de Bordeaux, Pole de Biologie et Pathologie, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Rhumatologie [Reims], Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), CHU Montpellier, Department of Clinical Hematology, Montpellier, France, Hospitalier et Universitaire de Pointe-à-Pitre (Oncologie Médicale), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CIBER Epidemiologia y Salud Pùblica [Madrid, Spain] (CIBERESP), Instituto de Salud Carlos III (ISC), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], Barretos Cancer Hospital [São Paulo, Brazil], Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary, Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Departement of Hematology, University Hospital, Bydgoszcz, Department of Hematology, Rigshospitalet, Copenhagen, Denmark, Department of Hematology, Jagiellonian University - Medical College, Gdynia Oncology Center, Gdynia and Department of Oncological Propedeutics, Genomic Oncology Area (GENYO), Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Department of Hematology, Insitute of Hematology and Transfusion Medicine, Warsa, Holycross Cancer Center of Kelce, Hematology Clinic, Kielce, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Department of Hematology, Medical University of Lodz, Departement of Experimental Hemato-Oncology, Medical University of Lubli (Polish Myeloma Study Group), Servicio de Hematología, Hospital Universitario 12 de Octubre [Madrid], Hematology and Medical Oncology Department, Hospital Morales Meseguer, Murcia (IMIB), Department of Biology, University of Pisa, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hematology Department, Teaching Hospital No1, Rzeszow, Teaching Hospital N°1, Haematology Department, University Hospital of Salamanca, Hematology Division Chaim Sheba Medical Center, Tel Hashomer, Department of Hematology Copernicus Hospital, Torun, Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Wroclaw Medical University, Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Icahn School of Medicine at Mount Sinai [New York] (MSSM), International Agency for Cancer Research (IACR), INSERM 1052, CNRS 5286, CRCL Lyon, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Centre de Recherche en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UPS), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Charleroi (Hématologie et pathologies de la coagulation), Centre Hospitalier Universitaire de Charleroi, Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Oncologie Génétique, de Prévention et Dépistage, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Département Universitaire Nice (Internal Medicine Department), Hôpital de Nice, Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne-Université Paris 13 (UP13), Laboratoire de diagnostic génétique et moléculaire, Centre Jean Perrin, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU Dijon, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Caen, Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de génomique du myélome [IUCT Oncopole, Toulouse], IUCT Oncopole - Institut Universitaire du Cancer de Toulouse, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CIBER de Epidemiología y Salud Pública (CIBERESP), Biomarkers and Susceptibility Unit, Catalan Institute of Oncology, Molecular Oncology Research Center [São Paulo, Brazil], Centro de Genomica e Investigacion Oncologica (GENYO), Hospital universitario 12 de Octubre, Holycross Cancer Center of Kielce, Hematology Clinic, Department of Laboratory Medicine Lunds University Hospital Lund, Cornell University [New York], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Laboratoire d'Hématologie [CHU Amiens], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier de Versailles André Mignot (CHV), Instituto de Salud Carlos III [Madrid] (ISC), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, Lund University [Lund], Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université catholique de Lille (UCL), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Pisa - Università di Pisa, Mines Paris - PSL (École nationale supérieure des mines de Paris), Wrocław Medical University, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes - Faculté de Médecine (UR Médecine), Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, Letter, [SDV]Life Sciences [q-bio], MEDLINE, Library science, Myeloma, World health, 03 medical and health sciences, 0302 clinical medicine, Multiple myeloma, immune system diseases, Political science, hemic and lymphatic diseases, Exome Sequencing, Genetics, Humans, Exome, Genetic Predisposition to Disease, Cancer genetics, Exome sequencing, Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS, Exosome Multienzyme Ribonuclease Complex, Extramural, Mieloma múltiple, French, Hematology, language.human_language, 3. Good health, Pedigree, [SDV] Life Sciences [q-bio], Exome/genetics, Exosome Multienzyme Ribonuclease Complex/genetics, Female, Genetic Predisposition to Disease/genetics, Germ-Line Mutation/genetics, Multiple Myeloma/genetics, Whole Exome Sequencing/methods, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Donation, language, Multiple Myeloma, Genètica, International agency
Abstract: French National Cancer Institute (INCA) and the Fondation Francaise pour la Recherche contre le Myelome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myelome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myelome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization
Published: 2019
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5. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial

Author: Margaret Macro, Andrew Ar Belch, Antoine Tinel, Nathalie Meuleman, Jean Yves Mary, Christian Rose, Paula Rodriguez-Otero, Philippe Moreau, Wenming Chen, Michel Attal, Marie Lorraine Chretien, William Renwick, Kihyun Kim, Meletios A. Dimopoulos, Eileen M Boyle, Xavier Leleu, Michael Sturniolo, Thierry Facon, Heinz Ludwig, Mara Silvia Monzini, Vanessa Houck, Elena Zamagni, Adrian Tempescul, Salomon Manier, Cyrille Hulin, Shien Guo, Mohamad Mohty, Bruno M. Costa, Facon T., Dimopoulos M.A., Meuleman N., Belch A., Mohty M., Chen W.-M., Kim K., Zamagni E., Rodriguez-Otero P., Renwick W., Rose C., Tempescul A., Boyle E., Manier S., Attal M., Moreau P., Macro M., Leleu X., Lorraine Chretien M., Ludwig H., Guo S., Sturniolo M., Tinel A., Silvia Monzini M., Costa B., Houck V., Hulin C., Yves Mary J., CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, National and Kapodistrian University of Athens (NKUA), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Cross Cancer Institute [Edmonton, AB, Canada], Service d'immunologie et hématologies biologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Capital Medical University, Beijing, Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Azienda Ospedaliero-Universitaria, Universidad de Navarra [Pamplona] (UNAV), Western Health The University of Melbourne, Université catholique de Lille (UCL), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), 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 Hôtel-Dieu de Nantes - Centre Hospitalier Universitaire de Nantes (Hôpital Hôtel-Dieu de Nantes - CHU de Nantes), Hôpital Universitaire de Caen, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Wilhelminenspital Vienna, Evidera, Celgene Corporation, Celgene International, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université 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), and Wilhelminenspital Vienna = Wilhelminen Hospital
Subjects: 0301 basic medicine, Male, Cancer Research, [SDV]Life Sciences [q-bio], Dexamethasone, 0302 clinical medicine, Clinical trials, Multiple myeloma, Antineoplastic Combined Chemotherapy Protocols, Stage (cooking), Lenalidomide, Melphalan, Aged, 80 and over, Frailty, Hematology, Middle Aged, 3. Good health, Thalidomide, [SDV] Life Sciences [q-bio], Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, Haematological diseases, Human, Adult, medicine.medical_specialty, FIRST (MM-020) trial, Frail Elderly, Newly diagnosed, Transplant ineligible, Anesthésiologie, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, In patient, Adverse effect, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, Clinical trial, Cancérologie, 030104 developmental biology, Charlson comorbidity index, Prednisone, business, Hématologie
Abstract: Patients with multiple myeloma are generally older and vary in fitness levels, which may influence the clinical benefit of treatment. Patients from the large, phase 3 FIRST trial in newly diagnosed multiple myeloma (NDMM) were retrospectively investigated to determine outcomes based on frailty using scores for age, Charlson Comorbidity Index (CCI), and Eastern Cooperative Oncology Group performance status (ECOG PS), instead of the EQ-5D quality-of-life questionnaire, as previously reported. ECOG PS (n = 1618) was investigated in frailty groups: frail (49%) and nonfrail (51%). Frail patients experienced worse progression-free and overall survival vs nonfrail patients. Prognostic assessment was improved when combining frailty and International Staging System stage (I/II vs III). Frail patients had a higher risk of developing grade 3/4 treatment-emergent adverse events. Treatment effects observed in the FIRST trial were confirmed per frailty group and per frailty and ISS group. The use of this ECOG PS–containing frailty scale as a predictive measure of clinical outcomes in patients with transplant-ineligible NDMM is supported by data from the FIRST trial. This score, based on age, CCI, and ECOG PS, can be easily replicated and may help design future myeloma studies in frail or nonfrail elderly patients., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019
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6. Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma

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

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

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

Author: Michel, Attal, Valerie, Lauwers-Cances, Cyrille, Hulin, Xavier, Leleu, Denis, Caillot, Martine, Escoffre, Bertrand, Arnulf, Margaret, Macro, Karim, Belhadj, Laurent, Garderet, Murielle, Roussel, Catherine, Payen, Claire, Mathiot, Jean P, Fermand, Nathalie, Meuleman, Sandrine, Rollet, Michelle E, Maglio, Andrea A, Zeytoonjian, Edie A, Weller, Nikhil, Munshi, Kenneth C, Anderson, Paul G, Richardson, Thierry, Facon, Hervé, Avet-Loiseau, Jean-Luc, Harousseau, Philippe, Moreau, P, Zunic, Pôle Institut Universitaire du Cancer - Oncopole [CHU Toulouse] (Pôle IUC - Oncopole), CHU Toulouse [Toulouse]-Oncopole de Toulouse, Service d'Epidémiologie, CHU Toulouse [Toulouse], Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pontchaillou [Rennes], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), 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, Hôpital Universitaire de Caen, 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), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire d'Hématologie biologique, Institut Curie [Paris], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Dana-Farber Cancer Institute [Boston], Hôpital Claude Huriez [Lille], CHU Lille, Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Hôtel-Dieu de Nantes, 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), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut Curie, Institut Jules Bordet, Hôpital Claude Huriez, and Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Male, Oncology, Follow-Up, Salvage therapy, Kaplan-Meier Estimate, Stem-Cell Transplantation, Dexamethasone, Bortezomib, 0302 clinical medicine, Maintenance therapy, Antineoplastic Combined Chemotherapy Protocols, Autologous Transplantation, Medicine, Lenalidomide, Multiple myeloma, Initial Treatment, Cancer, Phase-Iii, Induction Chemotherapy, General Medicine, Middle Aged, Daratumumab Monotherapy, Combined Modality Therapy, Thalidomide, 3. Good health, Hematologic Neoplasms, 030220 oncology & carcinogenesis, Female, Adults with multiple myeloma, Multiple Myeloma, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Transplantation, Autologous, Disease-Free Survival, Article, Maintenance Chemotherapy, 03 medical and health sciences, Internal medicine, Humans, Autologous transplantation, Aged, Salvage Therapy, Transplantation, Diagnosed Multiple-Myeloma, Prednisone Plus Thalidomide, business.industry, Elderly-Patients, medicine.disease, Surgery, Randomized Controlled-Trial, business, Stem Cell Transplantation, 030215 immunology
Abstract: International audience; BackgroundHigh-dose chemotherapy plus autologous stem-cell transplantation has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. However, promising data on the use of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) in this population have raised questions about the role and timing of transplantation.MethodsWe randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients). Patients in both groups received maintenance therapy with lenalidomide for 1 year. The primary end point was progression-free survival.ResultsMedian progression-free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone (50 months vs. 36 months; adjusted hazard ratio for disease progression or death, 0.65; P
Published: 2017
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11. Enhancing the diagnosis of fabry disease in cardiology with a targeted information: a before–after control–impact study

Author: Carole Brasse-Lagnel, Soumeya Bekri, Anne-Louise Savary, Paul Milliez, Rémy Morello, Fabien Labombarda, Unité de Biostatistique et de Recherche Clinique (UBRC), 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), Team 4 'NeoVasc' - INSERM U1245, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Caen, Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre hospitalier universitaire de Rouen, and Normandie Université (NU)
Subjects: Pediatrics, medicine.medical_specialty, Pathology, Screening test, medicine.medical_treatment, Impact study, Disease, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 030204 cardiovascular system & hematology, Left ventricular hypertrophy, 03 medical and health sciences, 0302 clinical medicine, Medicine, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Dried blood, Heart Failure and Cardiomyopathies, ComputingMilieux_MISCELLANEOUS, Fabry disease, business.industry, hereditary cardiomyopathy, Hypertrophic cardiomyopathy, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, 3. Good health, left ventricular hypertrophy, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cardiac monitoring, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Background Cardiac complications in Fabry disease are frequent and dominated by a high frequency of left ventricular hypertrophy; therefore, cardiologists may have an essential role in screening for this disease. Providing cardiologists with targeted information on Fabry disease would be valuable and could reduce both diagnostic and therapeutic delays. The aim of this study was to evaluate the efficiency of such strategy for Fabry screening. Methods We conducted a before–after control–impact study by comparing observations made before and after targeted information on Fabry disease among cardiologists. The information on Fabry disease consisted of (1) an educational booklet, (2) oral information and (3) screening kits. The programme was evaluated at the end of a 12-month study period. Results Forty-two cardiologists participated to this study. None of them had conducted screening test and new diagnostic for Fabry disease in the 3 years prior the information. After the information, screening with dried blood spots was performed in 55 patients (ranged 18–77 years, men: 39) with cardiac monitoring for supposed sarcomeric hypertrophic cardiomyopathy (n=41) or unexplained left ventricular hypertrophy (n=14) from January 2015 to January 2016. Two new cases of Fabry disease were diagnosed (3.4%) in two men (ages 58 and 51 years). The information was deemed relevant in both content and structure and was deemed useful for everyday practice. Conclusion Cardiologists valued the targeted information on Fabry disease. This information had a direct clinical impact by allowing the diagnosis of two new families with Fabry disease.
Published: 2017
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12. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group

Author: Hervé Tilly, Bertrand Coiffier, Vincent Delwail, Olivier Fitoussi, Christophe Fermé, Bernadette Corront, Corinne Haioun, Jean-Marc Schiano, Hassan Farhat, Christophe Fruchart, Hervé Ghesquières, Serge Bologna, Frederic Peyrade, Richard Delarue, Jean-François Emile, Jean Gabarre, Bachra Choufi, Margaret Macro, Laurent Pascal, Fabrice Jardin, Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Université de Poitiers-CHU de Poitiers, Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement ( UMRESTTE UMR T9405 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux ( IFSTTAR ), Institut Gustave Roussy ( IGR ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), Centre hospitalier d'Annecy, CH Annecy, Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Maison des Sciences de l'Homme et de l'Environnement Claude Nicolas Ledoux ( MSHE ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Hôpital Universitaire de Caen, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Immunologie ( EA 2686 ), Université de Lille, Droit et Santé, Service d'hématologie biologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Polyclinique Bordeaux Nord Aquitaine, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Laboratoire Chrono-environnement - UFC (UMR 6249) ( LCE ), Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Service d'immuno-hématologie pédiatrique [CHU Necker], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Poitiers - CHU de Poitiers, Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1) - Centre National de la Recherche Scientifique (CNRS), Hôpital Saint-Vincent de Paul, Département de médecine oncologique, Institut Gustave Roussy (IGR), Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon - Centre Hospitalier Lyon Sud [Pierre Bénite], Institut d'Electronique et de Télécommunications de Rennes (IETR), Université de Rennes 1 (UR1) - Institut National des Sciences Appliquées - Rennes (INSA Rennes) - SUPELEC - Centre National de la Recherche Scientifique (CNRS), Maison des Sciences de l'Homme et de l'Environnement Claude Nicolas Ledoux (MSHE), Centre National de la Recherche Scientifique (CNRS) - Université de Franche-Comté (UFC), Centre Léon Bérard [Lyon], Laboratoire d'Immunologie (EA 2686), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - AP-HP Hôpital Necker - Enfants Malades [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe d'étude des proliférations lymphoïdes, and Université de Rouen - Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Vincristine, Sialic Acid Binding Ig-like Lectin 2, Population, CHOP, Neutropenia, Ofatumumab, Antibodies, Monoclonal, Humanized, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, International Prognostic Index, Antineoplastic Agents, Immunological, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, education, Cyclophosphamide, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, education.field_of_study, business.industry, Antibodies, Monoclonal, Hematology, medicine.disease, Surgery, Regimen, Treatment Outcome, chemistry, Doxorubicin, 030220 oncology & carcinogenesis, Prednisone, Female, Lymphoma, Large B-Cell, Diffuse, business, Febrile neutropenia, 030215 immunology, medicine.drug
Abstract: Summary Background In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49–67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment. Methods For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 [day −7]) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days [day −7 to day −4]) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m 2 of intravenous doxorubicin, 400 mg/m 2 of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m 2 of oral prednisone on days 1–5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT01195714. Findings Between June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2–3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5–30·1). The 2-year overall survival was 64·7% (95% CI 55·3–72·7) and median overall survival was not reached (95% CI 30·2–not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients, grade 3–4 neutropenia was reported in 24 (21%) patients and thrombocytopenia in two (2%), during the treatment period. Grade 3–4 anaemia was reported in six (5%) patients; seven (6%) patients had one episode of febrile neutropenia. 17 (15%) of 115 patients in the modified intention-to-treat population had red blood cell transfusions and three (3%) had platelet transfusions. Interpretation Our result suggest that, in patients older than 80 years with DLBCL, ofatumumab and pre-phase treatment seem to improve overall survival compared with the previously reported data. The combination of pre-phase treatment, a monoclonal antibody against CD20, and miniCHOP can be considered a new treatment platform for use in randomised clinical trial design for DLBCL treatment in patients older than 80 years. Funding The Lymphoma Study Association, GlaxoSmithKline.
Published: 2017
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13. Bortezomib-doxorubicin-cyclophosphamide-dexamethasone induction followed by stem cell transplantation for primary plasma cell leukemia: a prospective phase II study of the IFM

Author: Royer, Bruno, Stéphane, Minvielle, Diouf, Momar, Roussel, Murielle, Karlin, Lionel, Hulin, Cyrille, Arnulf, Bertrand, Macro, Margaret, Sylvie, Cailleres, Brion, Annie, Bréchignac, Sabine, Karim, Beladj, Chrétien, Marie Lorraine, Wetterwald, Marc, Chaleteix, Carine, Tiab, Mourad, Leleu, Xavier, Frenzel, Laurent, Garderet, Laurent, Choquet, Sylvain, Fuzibet, Jean-Gabriel, Dauriac, Charles, Forneker, Luc-Matthieu, Benboubker, Lotfi, Facon, Thierry, Moreau, Philippe, Avet-Loiseau, Hervé, Marolleau, Jean-Pierre, CHU Amiens-Picardie, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de l'Innovation et Recherche Clinique, 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-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital universitaire de Lyon, Hôpital Universitaire de Lyon, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Universitaire de Caen, Hôpital Général Aix en Provence, Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Universitaire de Bobigny, Hôpital Universitaire de Créteil, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Général de Dunkerque, Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital Général de La Roche sur Yon, Facteurs de persistance des cellules leucémique - Equipe 3 (INSERM U 837), Service des Maladies du Sang, Hôpital Huriez, CHU Necker - Enfants Malades [AP-HP], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Universitaire Nice, Hôpital de Nice, Service Hématologie, CHU Pontchaillou [Rennes], Hôpital universitaire de Strasbourg, Hôpital Universitaire de Tours, Hôpital Claude Huriez [Lille], CHU Lille, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service clinique des Maladies du Sang, Bernardo, Elizabeth, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Hôpital Universitaire de Toulouse
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; PurposePrimary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in patients with pPCL to assess the efficacy of an alternate regimen that combines standard chemotherapy, a proteasome inhibitor, and high-dose melphalan and autologous stem cell transplantation (HDM/ASCT) followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance.Patients and MethodsPatients 70 years old and younger with newly diagnosed pPCL received four alternating cycles of bortezomib, dexamethasone plus doxorubicin or cyclophosphamide. Peripheral blood stem cells were collected from responding patients with < 1% of circulating plasma cells before HDM/ASCT. As consolidation, young patients received a reduced-intensity conditioning allograft, whereas the remaining patients underwent a second HDM/ASCT followed by 1 year of bortezomib, lenalidomide, dexamethasone. The primary end point was progression-free survival (PFS).ResultsForty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance).ConclusionIn this prospective trial in patients with pPCL, we show that bortezomib, dexamethasone plus doxorubicin or cyclophosphamide induction followed by transplantation induces high response rates and appears to significantly improve PFS.
Published: 2016
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14. Salvage Therapy Post Pomalidomide-Based Regimen in Relapsed/Refractory Myeloma

Author: Hervé Avet-Loiseau, Murielle Roussel, Michel Attal, Philippe Moreau, Philippe Rodon, Gerald Marit, Brigitte Kolb, Mamoun Dib, Olivier Decaux, Bruno Royer, Brigitte Pegourie, Marc Wetterwald, Marie-Odile Petillon, Anne Banos, Denis Caillot, Lionel Karlin, Mourad Tiab, Anne-Marie Stoppa, Sabine Brechignac, Guillemette Fouquet, Cyrille Hulin, Xavier Leleu, Margaret Macro, Laurent Garderet, Jean-Paul Fermand, Thierry Facon, Laurence Legros, Bertrand Arnulf, Lotfi Benboubker, Martine Escoffre, Claire Mathiot, Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Universitaire de Caen, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Laboratoire d'Hématologie biologique, Institut Curie, Service d'Hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Universitaire de Bobigny, Hôpital Général de La Roche sur Yon, Hôpital de Bayonne, CH de la Côte Basque, Hôpital Général de Dunkerque, Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Universitaire de Tours, 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 ), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Service d'Hématologie Clinique, Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Laboratoire d'Hématologie [Rangueil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Hôpital Claude Huriez [Lille], CHU Lille, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], 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), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], INSTITUT CURIE, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Universitaire de Vandoeuvre les Nancy, 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche en Cancérologie de Toulouse ( CRCT ), Université Toulouse III - Paul Sabatier ( UPS ), 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 ), Centre Hospitalier de la Côte Basque (CHCB), 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 ), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie Clinique (CHU de Dijon), 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), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire [Grenoble] (CHU), Intergroupe francophone du myélome (IFM), Service d'Hématologie [Bordeaux], CHU Bordeaux [Bordeaux], 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 Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'hématologie clinique (CHU d'Avicenne), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Hopital de Périgueux (CH Périgueux), Hopital de Périgueux, 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 de Médecine Onco-hématologie [La Roche sur Yon], Centre Hospitalier Universitaire de Nantes, Service hématologie Nice, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hématologie (CH de la Côte Basque), Service d'hématologie (CH de Dunkerque), Centre Hospitalier Dunkerque, Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Service d'Hématologie [CHRU Nancy], Département d’Hématologie Clinique [CHU Tours], Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Service d'hématologie adulte [Hôpital de Saint Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie [Nantes], 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), Oncologie hématologique et Thérapie Cellulaire (CHU Poitiers), Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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 Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Le CHCB, Centre Hospitalier de la Côte Basque, Service d'Hématologie Clinique [CHU Amiens], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, CHU Saint Louis [APHP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Oncology, Palliative care, Survival, [SDV]Life Sciences [q-bio], Salvage therapy, Disease, Biochemistry, Dexamethasone, 0302 clinical medicine, Stable Disease, Recurrence, Antineoplastic Combined Chemotherapy Protocols, Medicine, Multiple myeloma, Aged, 80 and over, 0303 health sciences, Hematology, General Medicine, Middle Aged, Thalidomide, 3. Good health, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, medicine.drug, Bendamustine, Adult, medicine.medical_specialty, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, 03 medical and health sciences, Internal medicine, Humans, 030304 developmental biology, Aged, Salvage Therapy, [ SDV ] Life Sciences [q-bio], business.industry, Disease progression, Cell Biology, Pomalidomide, medicine.disease, Regimen, 030104 developmental biology, Relapsed refractory, business, 030215 immunology
Abstract: Background. The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) has been proven effective and safe in patients with end-stage relapsed/refractory multiple myeloma (RRMM), otherwise characterized by a very poor outcome and short survival of less than a year. However, multiple myeloma remains incurable and relapses are inevitable even with pomalidomide-based regimen. It is thought that patients are back to unmet medical need after pomalidomide exposure, although the outcome after pomalidomide remains unknown. We sought to analyse the line of therapy in RRMM after Pom-Dex treatment, the response to further treatment line and survival post pomalidomide era. Methods. We included 134 patients from the 2 IFM studies (IFM2009-02 in end stage RRMM, n=84, median therapy 5 lines and IFM2010-02 in del17p and/or t(4;14) RRMM, n=50, median therapy 2 lines) treated with Pom-Dex. In both studies, patients received pomalidomide (oral 4mg daily) given either 21 days out of 28 or continuous and dexamethasone (oral 40mg weekly, but 20mg if >75 years old in the IFM 2010-02), given until progression. Overall, 95/135 patients (70%) received further therapy post Pom-Dex, 57/84 (68%) and 38/50 (76%) in IFM2009-02 and IFM2010-02 studies, respectively; the remaining patients had palliative care. Results. As a whole for the 95 patients, the median age was 60 (range 31-82), the M/F ratio was 1.5, t(4;14) was observed in 26/50 (52%) and del17p in 14/47 (30%). The post Pom-Dex regimens were very diverse, and varied significantly across the 2 trials; however, the regimens contained alkylating agents in 54% and 60% of patients in IFM2009-02 and IFM2010-02, respectively. The most prescribed alkylator was cyclophosphamide (60%) in IFM2010-02 while similar prescription of cyclophosphamide and bendamustine was observed in about 40% of patients in the IFM2009-02 study (p=0.032). Alkylating agents were administered primarily in a 3 drugs-based combination (or more) in IFM2010-02, 70%, versus in combination solely to dexamethasone for most patients in IFM2009-02, 60% (p=0.034). Amongst the combinations of alkylating agents, novel agents were considered in 55% versus 17.5% in the 2 studies, as expected considering that IFM2010-02 included patients exposed but not refractory to lenalidomide, while IFM2009-02 recruited essentially patients double refractory to lenalidomide and bortezomib (p When no alkylating agent was used, bortezomib plus dexamethasone, dexamethasone alone, or clinical trials were favoured, the latter in a lesser instance. An intensification was proposed in 8% of patients (n=8), with allogeneic transplantation in 3 patients. 27% and 29% responded to the post Pom-Dex regimen, with an extra 35% and 34% having stable disease in the 2 studies, respectively. With a median follow-up of 49 months (IFM2009-02) and 24 months (IFM2010-02), 77% and 52% of patients have died. The median PFS on Pom-Dex was approximately 5 months (CI95% 2.5;6.5) across the studies, with 20% of patients free of relapse beyond a year, similar to the post Pom-Dex phase, 5 months (2.9;7.0) and 4 months (2.2;5.7) in 2010-02 and 2009-02, with 29% and 13% of patients progression-free beyond one year, respectively. Importantly, the median OS of IFM2009-02 study (end stage RRMM, median 5 lines) for patients that had a post pomalidomide regimen was 20 months (14;26), with 30% of patients beyond 3 years, versus 13 months for the study as a whole (Leleu et al. Blood 2013) including patients considered in palliative care after Pom-Dex was stopped. This difference was not observed in IFM2010-02 to the same extent, in patients treated earlier with Pom-Dex but characterized with poor risk cytogenetic features, del17p and/or t(4;14), median OS of 14 months (9;18) across the 2 subgroups versus a median OS of 12 months and 9.8 months for the 2 subgroups in the study as a whole (Leleu et al. Blood 2015). Conclusion. Pom-Dex changed the paradigm in advanced RRMM with a prolonged PFS that translated into a prolonged OS. Importantly, OS was further improved when patients were offered a post pomalidomide therapy particularly in advanced RRMM with no poor risk cytogenetic features. Future studies might confirm the survival impact of pomalidomide used earlier in the disease course. The IFM2009-02 and 2010-02 trials were conducted with the support of Celgene Disclosures Karlin: BMS: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria. MACRO:celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees. Arnulf:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Stoppa:Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Legros:BMS: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; ARIAD: Speakers Bureau. Garderet:Bristol-Myers Squibb: Consultancy. Moreau:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Avet-Loiseau:Janssen: Research Funding; Celgene: Research Funding; Takeda: Research Funding. Attal:jansen: Honoraria; celgene: Membership on an entity's Board of Directors or advisory committees. Facon:Janssen: 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, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Leleu:Pierre Fabre: Honoraria; BMS: Honoraria; Novartis: Honoraria; TEVA: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; LeoPharma: Honoraria; Chugai: Honoraria.
Published: 2015
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15. Causes-of-death analysis of patients with cardiac resynchronization therapy: an analysis of the CeRtiTuDe cohort study

Author: Marijon, Eloi, Leclercq, Christophe, Narayanan, Kumar, Boveda, Serge, Klug, Didier, Lacaze-Gadonneix, Jonathan, Defaye, Pascal, Jacob, Sophie, Piot, Olivier, Deharo, Jean-Claude, Perier, Marie-Cécile, Mulak, Genevieve, Hermida, Jean-Sylvain, Milliez, Paul, Gras, Daniel, Cesari, Olivier, Hidden-Lucet, Françoise, Anselme, Frederic, Chevalier, Philippe, Maury, Philippe, Sadoul, Nicolas, Bordachar, Pierre, Cazeau, Serge, Chauvin, Michel, Empana, Jean-Philippe, Jouven, Xavier, Daubert, Jean-Claude, Le Heuzey, Jean-Yves, Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de cardiologie et maladies vasculaires, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Clinique Pasteur et Groupe Rythmologie Stimulation Cardiaque/SFC, Clinique Pasteur [Toulouse], Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Cardiac Stimulation and Rhythmology, CHU Grenoble, Radiobiologie et épidémiologie ( DRPH/SRBE ), Institut de Radioprotection et de Sûreté Nucléaire ( IRSN ), Médicaments : Dynamique Intracellulaire et Architecture Nucléaire ( MéDIAN ), Université de Reims Champagne-Ardenne ( URCA ) -Centre National de la Recherche Scientifique ( CNRS ), Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires ( LRI - EA4062 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Société française de cardiologie, Hôpital Universitaire d'Amiens, Hôpital Universitaire de Caen, Cardiopathies et mort subite, Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Clinique Saint Gatien, Département de Cardiologie et Centre de Référence pour les Maladies Cardiaques Héréditaires, CHU Pitié-Salpêtrière [APHP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Service de cardiologie [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Hôpital Est -Lyon, CHU Toulouse [Toulouse], Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Département de Rythmologie-Stimulation- Hôpital Saint-Joseph, Paris ( Département de Rythmologie-Stimulation ), Groupe Hospitalier Paris Saint-Joseph, Hôpital universitaire de Strasbourg, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de RadioBiologie et d'Epidémiologie (IRSN/DRPH/SRBE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Centre cardiologique du Nord (CCN), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires (LRI - EA4062), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Cardiopathies et mort subite [ERL 3147], Université de Nantes (UN)-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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de cardiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de Rythmologie-Stimulation- Hôpital Saint-Joseph, Paris (Département de Rythmologie-Stimulation), Groupe Hospitalier Paris Saint-Joseph (hpsj), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Radiobiologie et épidémiologie (DRPH/SRBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Médicaments : Dynamique Intracellulaire et Architecture Nucléaire (MéDIAN), Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]
Subjects: genetic structures, Sudden death, health services administration, Cardiac resynchronization, cardiovascular system, Cardioverter defibrillator, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Heart failure, cardiovascular diseases, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Competing risk, circulatory and respiratory physiology
Abstract: International audience; AIMS: The choice of resynchronization therapy between with (CRT-D) and without (CRT-P) a defibrillator remains a contentious issue. Cause-of-death analysis among CRT-P, compared with CRT-D, patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice. METHODS AND RESULTS: A total of 1705 consecutive patients implanted with a CRT (CRT-P: 535 and CRT-D: 1170) between 2008 and 2010 were enrolled in CeRtiTuDe, a multicentric prospective follow-up cohort study, with specific adjudication for causes of death at 2 years. Patients with CRT-P compared with CRT-D were older (P \textless 0.0001), less often male (P \textless 0.0001), more symptomatic (P = 0.0005), with less coronary artery disease (P = 0.003), wider QRS (P = 0.002), more atrial fibrillation (P \textless 0.0001), and more co-morbidities (P = 0.04). At 2-year follow-up, the annual overall mortality rate was 83.80 [95% confidence interval (CI) 73.41-94.19] per 1000 person-years. The crude mortality rate among CRT-P patients was double compared with CRT-D (relative risk 2.01, 95% CI 1.56-2.58). In a Cox proportional hazards regression analysis, CRT-P remained associated with increased mortality (hazard ratio 1.54, 95% CI 1.07-2.21, P = 0.0209), although other potential confounders may persist. By cause-of-death analysis, 95% of the excess mortality among CRT-P subjects was related to an increase in non-sudden death. CONCLUSION: When compared with CRT-D patients, excess mortality in CRT-P recipients was mainly due to non-sudden death. Our findings suggest that CRT-P patients, as currently selected in routine clinical practice, would not potentially benefit with the addition of a defibrillator
Published: 2015
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16. Increase of pulmonary artery wedge pressure above 15 mm Hg inpatients with pre-capillary pulmonary hypertension

Author: Thérèse Lognoné, Rémi Sabatier, Emmanuel Bergot, Julien Wain-Hobson, Ziad Dahdouh, Farzin Beygui, Vincent Roule, Mamadou Koné, Damien Legallois, Paul Milliez, Gilles Grollier, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), MTCT-Plus programme (ACONDA), MTCT-Plus programme, Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique (SEILIRM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de cardiologie et de pathologie vasculaire [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de pneumologie [CHU Caen], Service de cardiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), and Hôpital Universitaire de Caen
Subjects: medicine.medical_specialty, Cardiac output, [SDV]Life Sciences [q-bio], Heart failure, 030204 cardiovascular system & hematology, Pulmonary hypertension, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Pulmonary wedge pressure, ComputingMilieux_MISCELLANEOUS, Ejection fraction, business.industry, Central venous pressure, medicine.disease, 3. Good health, Preload, Pulmonary artery wedge pressure, medicine.anatomical_structure, 030228 respiratory system, Vascular resistance, Cardiology, Cardiology and Cardiovascular Medicine, business, Left ventricular diastolic dysfunction
Abstract: Aims Daily practice shows that patients with pre-capillary pulmonary hypertension (PH) may develop a secondary elevation of their pulmonary artery wedge pressure (PAWP) above the 15 mm Hg limit. This phenomenon has not been precisely described yet. We aimed at identifying factors present at initial diagnosis that could predict this secondary elevation of PAWP, its possible causes and impact on survival. Methods and results We included 90 patients followed between 2004 and 2011 in our center. At the end of follow-up (3.0 ± 1.6 years), patients were divided into two groups according to the successive PAWP measurements (always ≤ 15 mm Hg or > 15 mm Hg on at least one right heart catheterization (RHC)). Demographical, biological, echographic and hemodynamical data at first RHC were compared. Possible causes for PAWP > 15 mm Hg were searched. A Kaplan–Meier method was used to assess differences in survival. One third of our cohort developed an elevation of PAWP above 15 mm Hg and patients with idiopathic pulmonary arterial hypertension were at smaller risk (OR 0.20 [0.05–0.82]; p = 0.026). We did not identify any other baseline predictive factors. We highlighted several possible causes and factors that may unmask an underlying left ventricular diastolic dysfunction. Survival was not different between both groups (p = 0.42). Conclusion Secondary elevation of PAWP in pre-capillary PH was frequent but less observed in idiopathic PH. We detailed many possible causes that can be sought, many of which may be related to an underlying left ventricular diastolic dysfunction.
Published: 2014
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17. Impact of Poor Tolerance and Discontinuation of the Dexamethasone during Treatment with Lenalidomide-Dexamethasone in Relapsed and Refractory Multiple Myeloma

Author: Charles Lancesseur, Marie Lorraine Chretien, Murielle Roussel, Eileen M Boyle, Olivier Decaux, Guillemette Fouquet, Bertrand Arnulf, Hélène Demarquette, Morgane Nudel, Thierry Facon, Lionel Karlin, Margaret Macro, Xavier Leleu, Denis Caillot, Benjamin Hebraud, Cyrille Hulin, Stéphanie Guidez, Cécile Fohrer, Hôpital Claude Huriez [Lille], CHU Lille, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'immunologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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 ), Service d'hématologie biologique, Hôpital Universitaire de Caen, CHU Pontchaillou [Rennes], Centre Hospitalier de Valenciennes, 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 ), and Jonchère, Laurent
Subjects: Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], education, Immunology, Pharmacology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Adverse effect, health care economics and organizations, Dexamethasone, Multiple myeloma, 030304 developmental biology, Lenalidomide, 0303 health sciences, business.industry, Refractory Multiple Myeloma, Cell Biology, Hematology, medicine.disease, 3. Good health, Discontinuation, [SDV] Life Sciences [q-bio], business, 030215 immunology, medicine.drug
Abstract: Background. Lenalidomide plus Dexamethasone is approved at first relapse and beyond in Europe, and has transformed the prognosis of Myeloma in the relapse setting. Lenalidomide plus Dexamethasone is approved until progression, that could last for years, the median PFS in phase 3 studies being at 17 months at first relapse, but many patients eventually reach 5 to 7 years these days. Dexamethasone was showed to enhance lenalidomide-antitumor efficacy and to prolong the progression-free survival. However, long term exposure to dexamethasone is also known to be associated to an array of adverse events. Finally, IMiDs are known to act through immunomodulation a class-based mechanism. It is possible that lenalidomide might show efficacy on the long run without need to dexamethasone use, at least for some patients with myeloma. We sought to study the impact of dexamethasone discontinuation beyond six months and one year, and compare this analysis to patients treated on lenalidomide plus dexamethasone. Method. We have recruited 200 relapse refractory myeloma patients for this study from various IFM centers. The patients were to be older than 18 years old and treated with lenalidomide plus dexamethasone. We sought to study the impact of the various ways to use dexamethasone in the real life, and therefore dexamethasone was given according to physician decision. We identified groups according to dexamethasone given high dose (4 days 160mg total in a raw), given once a week at 40mg (considered standard dose), given at lower dose (considered low dose) and a group that had dexamethasone discontinued. Patients were not allowed to have other type of combination but lenalidomide plus dexamethasone. Result. A total of 200 patients were analyzed, median age of 57 years old (range 25-76). 17,5% patients had renal dysfunction at diagnosis. ISS was 2 for 20% and 3 for 20%. Approximately 10% had either del17p or t(4;14). 7% of patients had previous history of venous thrombosis before the treatment. Response rate, survival, including TTP, PFS, EFS and overall survival will be presented at ASH with updated follow-up. Conclusion. This study aims to investigate the importance of long run and exposure to Dexamethasone in the Lenalidomide-Dexamethasone regimen. We also wished to assess the optimal dose of dexamethasone that could be given to patients with prolonged exposure to lenalidomide plus dexamethasone. Disclosures Arnulf: Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. MACRO:millenium: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Leleu:LeoPharma: Honoraria; Pierre Fabre: Honoraria; BMS: Honoraria; Novartis: Honoraria; TEVA: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Chugai: Honoraria.
Published: 2015
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18. The Prognostic Value of Olfactory Dysfunction in Patients with COVID-19: The COVIDORA Study.

Author: Hamel AL, Delbos L, Natella PA, Radulesco T, Alexandru M, Bartaire E, Bartier S, Benoite G, Bequignon E, Castillo L, Canouï-Poitrine F, Carsuzaa F, Corré A, Coste A, Couloigner V, Daveau C, De Boissieu P, De Bonnecaze G, De Gabory L, Debry C, Deraedt S, Dufour X, El Bakkouri W, Gilain L, Hans S, Hautefort C, Hermann R, Jankowski R, La Croix C, Lecanu JB, Malard O, Michel J, Nguyen Y, Nevoux J, Papon JF, Patron V, Prigent M, Pruliere-Escabasse V, Renaud M, Rumeau C, Salmon D, Saroul N, Serrano E, Nhung Tran Khai C, Tringali S, Truy E, Vandersteen C, Verillaud B, Veil R, and Fieux M
Abstract: Background: Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between olfac-tory dysfunction (OD) and the evolution of disease severity. The main aim was to assess whether OD is a predictive factor of COVID-19 severity based on the patient's medical management (outpa-tient care, standard hospital admission, and ICU admission)., Methods: A national, prospective, mul-ticenter cohort study was conducted in 20 public hospitals and a public center for COVID-19 screen-ing. During the first wave of the pandemic, from 6 April to 11 May 2020, all patients tested positive for COVID-19 confirmed by RT-PCR underwent two follow-up ENT consultations within 10 days of symptom onset. The main outcome measures were the evolution of medical management (out-patient care, standard hospital admission, and ICU admission) at diagnosis and along the clinical course of COVID-19 disease., Results: Among 481 patients included, the prevalence of OD was 60.7%, and it affected mostly female patients (74.3%) under 65 years old (92.5%), with fewer comor-bidities than patients with normal olfactory function. Here, 99.3% (290/292) of patients with OD presented with non-severe COVID-19 disease. Patients reporting OD were significantly less hospi-talized than the ones managed as outpatients, in either a standard medical unit or an ICU. Conclu-sions: As regards the clinical course of COVID-19 disease, OD could predict a decreased risk of hospitalization during the first wave of the pandemic.
Published: 2024
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19. Association between acute complications in PMM2-CDG patients and haemostasis anomalies: Data from a multicentric study and suggestions for acute management.

Author: Wicker C, Roux CJ, Goujon L, de Feraudy Y, Hully M, Brassier A, Bérat CM, Chemaly N, Wiedemann A, Damaj L, Abi-Warde MT, Dobbelaere D, Roubertie A, Cano A, Arion A, Kaminska A, Da Costa S, Bruneel A, Vuillaumier-Barrot S, Boddaert N, Pascreau T, Borgel D, Kossorotoff M, Harroche A, and de Lonlay P
Subjects: Retrospective Studies, Child, Antithrombins, Hemostasis, Factor XI, Protein C, Humans, Hemorrhage, Congenital Disorders of Glycosylation pathology, Stroke, Thrombosis, Phosphotransferases (Phosphomutases) deficiency
Abstract: Objectives: Patients with PMM2-CDG develop acute events (stroke-like episodes (SLEs), thromboses, haemorrhages, seizures, migraines) associated with both clotting factors (factor XI) and coagulation inhibitors (antithrombin, protein C and protein S) deficiencies. The aim of the study was to correlate acute events to haemostasis and propose practical guidelines., Methods: In this multicentric retrospective study, we evaluated clinical, radiological, haemostasis and electroencephalography data for PMM2-CDG patients hospitalized for acute events. Cerebral events were classified as thrombosis, haemorrhage, SLE, or "stroke mimic" (SM: normal brain imaging or evoking a migraine)., Results: Thirteen patients had a total of 31 acute episodes: 27 cerebral events with 7 SLEs, 4 venous thromboses, 4 haemorrhages (3 associated with thrombosis), 15 SMs at a mean age of 7.7 years; 4 non-cerebral thromboses, one of which included bleeding. A trigger was frequently involved (infection, head trauma). Although sometimes normal at baseline state, factor XI, antithrombin and protein C levels decreased during these episodes. No correlation between haemostasis anomalies and type of acute event was found., Discussion: Acute events in PMM2-CDG are not negligible and are associated with haemostasis anomalies. An emergency protocol is proposed for their prevention and treatment (https://www.filiere-g2m.fr/urgences). For cerebral events, brain Magnetic Resonance Imaging with perfusion weight imaging and diffusion sequences, electroencephalogram and haemostasis protein levels guide the treatment: anticoagulation, antithrombin or fresh frozen plasma supplementation, antiepileptic therapy. Preventing bleeding and thrombosis is required in cases of surgery, prolonged immobilization, hormone replacement therapy., Conclusion: Acute events in PMM2-CDG are associated with abnormal haemostasis, requiring practical guidance., Competing Interests: Declaration of Competing Interest The authors Camille Wicker, Charles-Joris Roux, Louise Goujon, Yvan De Feraudy, Marie Hully, Anais Brassier, Claire-Marine Bérat, Nicole Chémaly, Arnaud Wiedemann, Lena Damaj, Marie-Thérèse Abi-Warde, Dries Dobbelaere, Agathe Roubertie, Aline Cano, Alina Arion, Anna Kaminska, Sabrina Da Costa, Arnaud Bruneel, Sandrine Vuillaumier, Nathalie Boddaert, Delphine Borgel, Tiffany Pascreau, Manoelle Kossorotoff, Annie Harroche, and P de Lonlay declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)
Published: 2023
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20. [Impact of pelvic floor educational sessions on teenage girls].

Author: Pizzoferrato AC, Arzel O, Reboursière E, Rousseau M, and Blanchard V
Subjects: Adolescent, Female, Humans, Pelvic Floor, Personal Satisfaction, Surveys and Questionnaires, Pelvic Floor Disorders, Urinary Incontinence
Abstract: Introduction: Our objective was to evaluate the impact of pelvic floor educational sessions on teenage girls about their general knowledge of pelvic floor disorders (PFD) and the anatomy of the pelvic floor., Material: Educational sessions were offered to teenage girls from middle and high schools in the city of Caen. Each session included pelvic floor anatomy, urinary and digestive physiology as well as situations that favor PFD. At the beginning and end of the session, the participants received a questionnaire on their knowledge and questions concerning their satisfaction were asked at the end of the session. A questionnaire was sent at 2 months to assess the changes in their urinary and digestive habits as well as the dissemination of information to those around them., Results: One hundred and five teenage girls, average age 15, participated in these sessions; 61% responded at 2 months. The educational sessions have significantly improved knowledge about the pelvic floor. After the sessions, 92% and 52% reported having changed their urinary and defecatory habits. Participants found the sessions very useful and all participants recommended these sessions to a friend., Conclusion: Pelvic floor educational sessions improve the knowledge of teenage girls and limit behaviors that favor PFD. Teenage satisfaction is important and the dissemination of information is high. A pelvic floor educational program in schools could help limit risky behaviors for the pelvic floor., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)
Published: 2022
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21. [Pelvic floor disorders: What do adolescents and young women know? A literature review].

Author: Mouadil M, Blanchard V, Fauvet R, Dehaene A, and Pizzoferrato AC
Subjects: Adolescent, Cross-Sectional Studies, Female, Humans, Pelvic Floor, Perineum, Surveys and Questionnaires, Pelvic Floor Disorders complications, Urinary Incontinence etiology, Urinary Incontinence therapy
Abstract: Aim: To assess the knowledge of adolescent girls and young women on pelvic-perineal disorders (PPD)., Method: We searched on PubMed, Cochrane Library, Kinédoc and Semantic Scholar databases using the MeSH keywords: "knowledge" "awareness" "surveys" "young women" "pelvic floor" "adolescent" "teenager" "athletic injury" "urinary incontinence". The articles had to have been published within the last 15 years, written in French or English, and deal with the state of knowledge of adolescents and young women concerning the perineal sphere using questionnaires., Results: A total of 8 studies were included in the review, 5 cross-sectional studies and 3 intervention studies. The knowledge of adolescent girls and young women interviewed about the anatomy of the pelvic floor, its function, and risk factors for PPD was low. The majority of the participants wanted more information about the pelvic floor. Two studies that conducted an educational intervention showed a significant improvement in knowledge., Conclusion: Knowledge of pelvic-perineal disorders and pelvic floor function is poor in adolescent girls and young women. To better assess them, it would be necessary to validate a questionnaire containing all the items about knowledge., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
Published: 2022
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22. [The use of pessaries for treatment of pelvic organ prolapse: A survey from gynecologists and urologists residents].

Author: Martin-Lasnel M, Nyangoh-Timoh K, Fauvet R, and Pizzoferrato AC
Subjects: Aged, Female, Humans, Pessaries, Quality of Life, Surveys and Questionnaires, Treatment Outcome, Urologists, Gynecology, Pelvic Organ Prolapse therapy
Abstract: Introduction: Pelvic organ prolapse (POP) is a common condition responsible for symptoms that significantly affect the quality of life in women. Despite its effectiveness, low cost and minor side effects, the pessary is little used in France. The objective of our study was to assess the knowledge, training and practices of residents regarding pessaries., Material and Methods: This survey was conducted among residents in obstetrics gynecology, medical gynecology and urology in France between March and September 2020., Results: During the study period, 328 interns responded to the questionnaires. The majority of residents (52.1%) reported never having attended a consultation specializing in pelvicperineology. Only 31.7% felt comfortable having a pessary inserted. According to them, the pessary was indicated in 3 main situations: in case of contraindication to surgery (80%), while awaiting surgery (79%) and in women over 70 years old (62%). The pessary could be offered to all women for only 46.9% of them. Almost 53% of residents reported ignoring the main complications of pessaries and 83.5% felt they needed further training on the subject., Conclusion: Interns seem to be generally aware of the use of the pessary. Their knowledge of the indications, complications or even monitoring leads us to believe that it is essential to promote their training so that the pessary becomes an integral part of the first-line therapeutic arsenal in the event of POPs., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
Published: 2021
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23. [Benefits of pelvic floor education in perineal re-education in women].

Author: Blanchard V, Nyangoh Timoh K, Bruyère F, Fritel X, and Pizzoferrato AC
Subjects: Adult, Female, Humans, Middle Aged, Patient Education as Topic, Surveys and Questionnaires, Treatment Outcome, Exercise Therapy methods, Pelvic Floor physiology, Pelvic Floor Disorders therapy, Quality of Life
Abstract: Aim: Evaluate the impact of pelvic floor education on the symptoms of female patients referred for pelvic floor muscle training (PFMT)., Methods: Forty female patients suffering from pelvic floor disorders and referred to independent practice for PFME between February and May 2019 answered a survey on symptoms and quality of life before PFME, after four sessions of pelvic floor education and at the end of PFME. The ICIQ-SF, USP, Contilife, PDFI 20, Kess, and Wexner scores were used to evaluate the results. The protocol consisted in four initial sessions of pelvic floor education including information on each field of perineology ; the fifth session was dedicated to visual feedback using a mirror ; the following five sessions were tailored according to the care objectives established based on the initial assessment., Results: The scores were significantly improved after the four initial sessions of pelvic floor education. The improvement was significant at the end of the re-education program. The PFDI-20 score dropped from 66,9 to 20,9 (P=0,002), the ICIQ-SF score from 8,4 to 1,5 (P<10 -3 ), the Wexner score from 7,4 to 5,1 (P<10 -3 ) and the Kess score from 14,2 to 8,7 (P=0,05)., Conclusion: The results showed that female patients undergoing perineal re-education including pelvic floor education sessions show a significant improvement in their symptoms already immediately after the pelvic floor education sessions., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
Published: 2020
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24. Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn's Disease in Sustained Remission.

Author: Reenaers C, Mary JY, Nachury M, Bouhnik Y, Laharie D, Allez M, Fumery M, Amiot A, Savoye G, Altwegg R, Devos M, Malamut G, Bourreille A, Flourie B, Marteau P, Vuitton L, Coffin B, Viennot S, Lambert J, Colombel JF, and Louis E
Subjects: Adult, Belgium, Female, Follow-Up Studies, France, Humans, Male, Prospective Studies, Recurrence, Treatment Outcome, Crohn Disease drug therapy, Crohn Disease pathology, Gastrointestinal Agents administration & dosage, Infliximab administration & dosage
Abstract: Background & Aims: Little is known about long-term outcomes of patients with Crohn's disease (CD) after infliximab withdrawal. We aimed to describe the long-term outcomes of patients with CD in clinical remission after infliximab treatment was withdrawn., Methods: We performed a retrospective analysis of data from the 115 patients included in the infliximab discontinuation in patients with CD in stable remission on combined therapy with antimetabolites (STORI) study, performed at 20 centers in France and Belgium from March 2006 through December 2009. The STORI cohort was a prospective analysis of risk and factors associated with relapse following withdrawal of maintenance therapy with infliximab, maintained on antimetabolites, while in clinical remission. We collected data from the end of the study until the last available follow-up examination on patient surgeries, new complex perianal lesions (indicating major complications), and need for and outcomes of restarting therapy with infliximab or another biologic agent. The de-escalation strategy was considered to have failed when a major complication or infliximab restart failure occurred., Results: Of the 115 patients initially included, data from 102 patients (from 19 of the 20 study centers) were included in the final analysis. The median follow-up time was 7 years. Twenty-one percent of the patients did not restart treatment with infliximab or another biologic agent and did not have a major complication 7 years after infliximab withdrawal (95% CI, 13.1-30.3). Among patients who restarted infliximab, treatment failed for 30.1% 6 years after restarting (95% CI, 18.5-42.5). Overall, at 7 years after stopping infliximab therapy, major complications occurred in 18.5% of patients (95% CI, 10.2-26.8) whereas 70.2% of patients had no failure of the de-escalation strategy (95% CI, 60.2-80.1). Factors independently associated with major complications were upper-gastrointestinal location of disease, white blood cell count ≥ 5.0 × 10 9 /L, and hemoglobin level ≤12.5 g/dL at the time of infliximab withdrawal. Patients with at least 2 of these factors had a more than 40% risk of major complication in the 7 years following infliximab withdrawal., Conclusions: In a long-term follow-up of the STORI cohort (7 years) one fifth of the patients did not restart infliximab or another biologic agent and did not develop major complications. Seventy percent of patients had no failure of the de-escalation strategy (no major complication and no failure of infliximab restart)., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Published: 2018
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25. Primary Progressive Aphasia in the Network of French Alzheimer Plan Memory Centers.

Author: Magnin E, Démonet JF, Wallon D, Dumurgier J, Troussière AC, Jager A, Duron E, Gabelle A, de la Sayette V, Volpe-Gillot L, Tio G, Evain S, Boutoleau-Bretonnière C, Enderle A, Mouton-Liger F, Robert P, Hannequin D, Pasquier F, Hugon J, and Paquet C
Subjects: Aged, Aged, 80 and over, Alzheimer Disease cerebrospinal fluid, Aphasia, Primary Progressive cerebrospinal fluid, Cohort Studies, Databases, Factual trends, Female, France epidemiology, Humans, Male, Middle Aged, Prospective Studies, Retrospective Studies, Alzheimer Disease diagnosis, Alzheimer Disease epidemiology, Aphasia, Primary Progressive diagnosis, Aphasia, Primary Progressive epidemiology, Secondary Care Centers trends, Tertiary Care Centers trends
Abstract: Background: Few demographical data about primary progressive aphasia (PPA) are available, and most knowledge regarding PPA is based on tertiary centers' results., Objective: Our aims were to describe demographical characteristics of the PPA population in a large sample of PPA patients from the network of French Alzheimer plan memory centers (Sample 1), and to describe the stratification of cerebrospinal fluid (CSF) biomarkers in two different samples of PPA patients (Samples 2 and 3)., Methods: All registered PPA patients in the French Alzheimer's disease (AD) databank (Sample 1: n = 2,035) and a subsample (Sample 2: n = 65) derived from a multicentric prospective cohort with CSF biomarker analysis were analyzed. A multicentric retrospective cohort from language expert tertiary centers (Sample 3: n = 97) with CSF biomarker analysis was added. Sample 3 was added to replicate the CSF results of the Sample 2 and to evaluate repartition of AD pathology in the three variant of PPA according to the latest classification., Results: Non-Fluent/Agrammatic, Logopenic, and Unclassifiable PPA patients (NF/A-Logo-Unclass PPA) were older and more frequent than Semantic PPA patients (2.2 versus 0.8/100,000 inhabitants; p < 0.00001). Male predominance occurred after the age of 80 (p < 0.00001). A higher level of education was observed in the PPA population compared to a typical amnesic AD group. No demographical significant difference between PPA due to AD and not due to AD was observed. The Logopenic variant was most frequent with 85% of AD CSF biomarker profiles (35% in NF/A PPA; 20% in Semantic PPA)., Conclusion: PPA occurs also in an elderly population, especially in male patients over 80. CSF biomarkers are useful to stratify PPA. The epidemiology of PPA should be further investigated to confirm gender and cognitive reserve role in PPA to better understand the factors and mechanisms leading to this language-predominant deficit during neurodegenerative diseases.
Published: 2016
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26. In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase II study.

Author: Leruez-Ville M, Ghout I, Bussières L, Stirnemann J, Magny JF, Couderc S, Salomon LJ, Guilleminot T, Aegerter P, Benoist G, Winer N, Picone O, Jacquemard F, and Ville Y
Subjects: Acyclovir administration & dosage, Acyclovir therapeutic use, Adult, Antiviral Agents administration & dosage, Cytomegalovirus Infections congenital, Cytomegalovirus Infections diagnostic imaging, Female, Fetal Blood virology, Fetal Diseases diagnostic imaging, Fetal Diseases drug therapy, Fetal Therapies, Humans, Infant, Newborn, Platelet Count, Pregnancy, Pregnancy Complications, Infectious diagnostic imaging, Pregnancy, High-Risk, Ultrasonography, Prenatal, Valacyclovir, Valine administration & dosage, Valine therapeutic use, Viral Load, Acyclovir analogs & derivatives, Antiviral Agents therapeutic use, Cytomegalovirus Infections drug therapy, Pregnancy Complications, Infectious drug therapy, Valine analogs & derivatives
Abstract: Background: Congenital infection with human cytomegalovirus is a major cause of morbidity and mortality. A randomized controlled trial showed that high-dosage valacyclovir prevents cytomegalovirus disease in transplant recipients. Fetuses showing ultrasound features of infection are at high risk of being symptomatic at or before birth. In a pilot study, oral administration of high-dosage valacyclovir to mothers significantly decreased viral load and produced therapeutic concentrations in the blood of infected fetuses. A randomized controlled trial comparing prenatal treatment with valacyclovir against placebo in infected fetuses failed to recruit because women declined randomization. Randomized controlled trials in fetal medicine have often proven unacceptable by women who decline termination of pregnancy and are not prepared to resign themselves to the odds of the natural history of the disease., Objective: We evaluated the efficacy of oral valacyclovir, 8 g daily, for pregnant women carrying a symptomatic cytomegalovirus-infected fetus, targeting a high-risk group for developing both neurosensory and neurological impairment., Study Design: We designed a multicenter, open-label, phase II study with 1 arm, using one of Simon's optimal 2-stage designs. Symptomatic fetuses were defined by the presence of measurable extracerebral or mild cerebral ultrasound symptoms. They were treated in utero from prenatal diagnosis at a median of 25.9 weeks' gestation until delivery or termination of pregnancy. Fetuses with severe brain anomalies on ultrasound were not included as were cases completely asymptomatic at presentation, because treatment was unlikely to modify either outcome. The primary endpoint was the proportion of asymptomatic neonates born to treated mothers., Results: At the interim analysis, 8 of 11 women delivered an asymptomatic neonate (required: ≥7). In step 2, 32 additional cases were included for a total of 43; the final number of asymptomatic neonates was 34, more than the 31 required to indicate efficacy according to the Simon 2-stage design. They remained asymptomatic at 12 months. High-dosage valacyclovir given for a median of 89 days to pregnant women carrying a moderately infected fetus was efficient at giving birth to asymptomatic neonates. Fetal blood viral loads decreased and platelet counts increased, both significantly (P = .01 and P < .001, respectively), between treatment initiation and birth after treatment completion, regardless of duration of fetal infection. Compared with a historical cohort obtained by a metaanalysis of the literature, the use of valacyclovir (8 g daily) significantly increased the proportion of asymptomatic neonates from 43% without treatment to 82% with treatment. Although the pill burden was high (16 pills a day) adherence to treatment was >90%. Finally, valacyclovir at this high dosage was extremely well tolerated., Conclusion: Our results indicate that high-dosage valacyclovir given in pregnancy is effective for improving the outcome of moderately symptomatic infected fetuses. Although this study is not a randomized controlled trial, this is the first study reporting the efficacy of an antiviral drug to treat cytomegalovirus-infected fetuses. Moreover, this first study will allow new trials to be conducted, using valacyclovir as a baseline safe and effective treatment in pregnancy, to be compared to the new emerging and more potent anticytomegalovirus drugs that have not currently been tested in pregnancy., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2016
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27. Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study.

Author: Sitbon O, Jaïs X, Savale L, Cottin V, Bergot E, Macari EA, Bouvaist H, Dauphin C, Picard F, Bulifon S, Montani D, Humbert M, and Simonneau G
Subjects: Adolescent, Adult, Aged, Bosentan, Drug Therapy, Combination methods, Epoprostenol administration & dosage, Female, Follow-Up Studies, Humans, Male, Middle Aged, Pilot Projects, Piperazines administration & dosage, Prognosis, Purines administration & dosage, Registries, Retrospective Studies, Sildenafil Citrate, Sulfonamides administration & dosage, Sulfones administration & dosage, Treatment Outcome, Young Adult, Antihypertensive Agents administration & dosage, Hypertension, Pulmonary drug therapy
Abstract: Patients with severe pulmonary arterial hypertension (PAH) in New York Heart Association (NYHA) functional class (FC) III/IV have a poor prognosis, despite survival benefits being demonstrated with intravenous epoprostenol. In this pilot study, the efficacy and safety of a triple combination therapy regimen in patients with severe PAH was investigated. Data from newly diagnosed NYHA FC III/IV PAH patients (n=19) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry. Significant improvements in 6-min walk distance and haemodynamics were observed after 4 months' triple combination therapy in 18 patients (p<0.01); 17 patients had improved to NYHA FC I or II. One patient was not included in the month 4 assessment (due to an emergency lung transplant in month 3). At the final evaluation (mean ± sd 32 ± 19 months), all 18 patients had sustained clinical and haemodynamic improvement. Overall survival estimates for the triple combination cohort were 100% at 1, 2 and 3 years. Expected survival calculated from the French equation was 75% (95% CI 68-82%), 60% (95% CI 50-70%) and 49% (95% CI 38-60%) at 1, 2 and 3 years, respectively. This pilot study provides preliminary evidence of the long-term benefits of upfront triple combination therapy in patients with severe PAH., (©ERS 2014.)
Published: 2014
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28. Prognostic impact of major bleeding in patients with acute coronary syndromes.A systematic review and meta-analysis.

Author: Hamon M, Filippi-Codaccioni E, Riddell JW, and Lepage O
Abstract: Aims: The causative relationship between major bleeding in acute coronary syndromes (ACS) and the increase in mortality and morbidity has frequently been suggested in recent pharmaco-invasive trials and registries. However, the magnitude of this increased risk is the subject of debate. In order to determine the prognostic significance of major bleeding in ACS, we have conducted a systematic review and meta-analysis., Methods and Results: Databases were searched for articles published up to March 2007. Any study, either retrospective or prospective, assessing the impact of major bleeding in patients with ACS was included if all-cause mortality was reported as an outcome measure.Data from 10 studies involving a total of 133,597 patients with ACS at baseline, of whom 3,644 had major bleeding (2.7%) were included in a meta-analysis using a random-effects model. An overall pooled relative risk (RR) mortality increase of 7.6 (95% CI; 5.5-10.4) was found in patients with major bleeding. Although most of the 95% confidence intervals (CIs) for the primary studies overlapped, some heterogeneity was observed (Chi2 for heterogeneity, P <0.0001), hence the need for the random-effects meta-analysis. However, the overall effect was highly significant (Z=12.65; P <0.00001). Major bleeding in ACS was also associated with a statistically significant increase in the secondary endpoints assessed including acute myocardial infarction (AMI), and stroke., Conclusions: This meta-analysis indicates that major bleeding in patients with ACS is a strong predictor of in-hospital or 30-day death and AMI. The pooled estimates presented should alert clinicians and interventionalists to the importance of prevention of major bleeding in patients hospitalised with ACS.
Published: 2007
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28 results on '"Hôpital Universitaire de Caen"'

1. Comparative study of changes in maternal and perinatal morbidity inequalities among migrant and native women over time, between 2008 and 2014 in France

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

3. Comparative study between women born in France and migrant women with regard to their mode of delivery

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

5. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial

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

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

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

9. Heavy + light chain analysis to assign myeloma response is analogous to the IMWG response criteria

10. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma

11. Enhancing the diagnosis of fabry disease in cardiology with a targeted information: a before–after control–impact study

12. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group

13. Bortezomib-doxorubicin-cyclophosphamide-dexamethasone induction followed by stem cell transplantation for primary plasma cell leukemia: a prospective phase II study of the IFM

14. Salvage Therapy Post Pomalidomide-Based Regimen in Relapsed/Refractory Myeloma

15. Causes-of-death analysis of patients with cardiac resynchronization therapy: an analysis of the CeRtiTuDe cohort study

16. Increase of pulmonary artery wedge pressure above 15 mm Hg inpatients with pre-capillary pulmonary hypertension

17. Impact of Poor Tolerance and Discontinuation of the Dexamethasone during Treatment with Lenalidomide-Dexamethasone in Relapsed and Refractory Multiple Myeloma

18. The Prognostic Value of Olfactory Dysfunction in Patients with COVID-19: The COVIDORA Study.

19. Association between acute complications in PMM2-CDG patients and haemostasis anomalies: Data from a multicentric study and suggestions for acute management.

20. [Impact of pelvic floor educational sessions on teenage girls].

21. [Pelvic floor disorders: What do adolescents and young women know? A literature review].

22. [The use of pessaries for treatment of pelvic organ prolapse: A survey from gynecologists and urologists residents].

23. [Benefits of pelvic floor education in perineal re-education in women].

24. Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn's Disease in Sustained Remission.

25. Primary Progressive Aphasia in the Network of French Alzheimer Plan Memory Centers.

26. In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase II study.

27. Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study.

28. Prognostic impact of major bleeding in patients with acute coronary syndromes.A systematic review and meta-analysis.

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28 results on '"Hôpital Universitaire de Caen"'

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