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1. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Author

Francine Garnache-Ottou, Chrystelle Vidal, Sabeha Biichlé, Florian Renosi, Eve Poret, Maïder Pagadoy, Maxime Desmarets, Anne Roggy, Estelle Seilles, Lou Soret, Françoise Schillinger, Sandrine Puyraimond, Tony Petrella, Claude Preudhomme, Christophe Roumier, Elisabeth A. MacIntyre, Véronique Harrivel, Yohan Desbrosses, Bérengère Gruson, Franck Geneviève, Sylvain Thepot, Yuriy Drebit, Thibaut Leguay, François-Xavier Gros, Nicolas Lechevalier, Pascale Saussoy, Véronique Salaun, Edouard Cornet, Zehaira Benseddik, Richard Veyrat-Masson, Orianne Wagner-Ballon, Célia Salanoubat, Marc Maynadié, Julien Guy, Denis Caillot, Marie-Christine Jacob, Jean-Yves Cahn, Rémy Gressin, Johann Rose, Bruno Quesnel, Estelle Guerin, Franck Trimoreau, Jean Feuillard, Marie-Pierre Gourin, Adriana Plesa, Lucile Baseggio, Isabelle Arnoux, Norbert Vey, Didier Blaise, Romaric Lacroix, Christine Arnoulet, Blandine Benet, Véronique Dorvaux, Caroline Bret, Bernard Drenou, Agathe Debliquis, Véronique Latger-Cannard, Caroline Bonmati, Marie-Christine Bene, Pierre Peterlin, Michel Ticchioni, Pierre-Simon Rohrlich, Anne Arnaud, Stefan Wickenhauser, Valérie Bardet, Sabine Brechignac, Benjamin Papoular, Victoria Raggueneau, Jacques Vargaftig, Rémi Letestu, Daniel Lusina, Thorsten Braun, Vincent Foissaud, Jérôme Tamburini, Hind Bennani, Nicolas Freynet, Catherine Cordonnier, Magali Le Garff-Tavernier, Nathalie Jacques, Karim Maloum, Damien Roos-Weil, Didier Bouscary, Vahid Asnafi, Ludovic Lhermitte, Felipe Suarez, Etienne Lengline, Frédéric Féger, Giorgia Battipaglia, Mohamad Mohty, Sabrina Bouyer, Ouda Ghoual, Elodie Dindinaud, Caroline Basle, Mathieu Puyade, Carinne Lafon, Thierry Fest, Mikael Roussel, Xavier Cahu, Elsa Bera, Sylvie Daliphard, Fabrice Jardin, Lydia Campos, Françoise Solly, Denis Guyotat, Anne-Cécile Galoisy, Alice Eischen, Caroline Mayeur-Rousse, Blandine Guffroy, Christian Recher, Marie Loosveld, Alice Garnier, Vincent Barlogis, Maria Alessandra Rosenthal, Sophie Brun, Nathalie Contentin, Sébastien Maury, Mary Callanan, Christine Lefebvre, Natacha Maillard, Patricia Okamba, Christophe Ferrand, Olivier Adotevi, Philippe Saas, Fanny Angelot-Delettre, Delphine Binda, and Eric Deconinck

Subjects
Specialties of internal medicine, RC581-951
Abstract

Abstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

Published
2019
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2. Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape

Author

Loria Zalmaï, Pierre-Julien Viailly, Sabeha Biichle, Meyling Cheok, Lou Soret, Fanny Angelot-Delettre, Tony Petrella, Marie-Agnès Collonge-Rame, Estelle Seilles, Sandrine Geffroy, Eric Deconinck, Etienne Daguindau, Sabrina Bouyer, Elodie Dindinaud, Victor Baunin, Magali Le Garff-Tavernier, Damien Roos-Weil, Orianne Wagner-Ballon, Véronique Salaun, Jean Feuillard, Sophie Brun, Bernard Drenou, Caroline Mayeur-Rousse, Patricia Okamba, Véronique Dorvaux, Michel Tichionni, Johann Rose, Marie Thérèse Rubio, Marie Christine Jacob, Victoria Raggueneau, Claude Preudhomme, Philippe Saas, Christophe Ferrand, Olivier Adotevi, Christophe Roumier, Fabrice Jardin, Francine Garnache-Ottou, and Florian Renosi

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

Neoplasms involving plasmacytoid dendritic cells (pDC) include blastic pDC neoplasms (BPDCN) and other pDC proliferations, where pDC are associated with myeloid malignancies: most frequently chronic myelomonocytic leukemia (CMML) but also acute myeloid leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDC in pDC-AML, and their link with the CD34+ blasts, monocytes or conventional DC (cDC) associated in the same sample, by phenotypic and molecular analyses (targeted next-generation sequencing, 70 genes). We compared 15 pDCAML at diagnosis with 21 BPDCN and 11 normal pDC from healthy donors. CD45low CD34+ blasts were found in all cases (10-80% of medullar cells), associated with pDC (4-36%), monocytes in 14 cases (1-10%) and cDC (two cases, 4.8-19%). pDC in pDC-AML harbor a clearly different phenotype from BPDCN: CD4+ CD56– in 100% of cases, most frequently CD303+, CD304+ and CD34+; lower expression of cTCL1 and CD123 with isolated lymphoid markers (CD22/CD7/CD5) in some cases, suggesting a prepDC stage. In all cases, pDC, monocytes and cDC are neoplastic since they harbor the same mutations as CD34+ blasts. RUNX1 is the most commonly mutated gene: detected in all AML with minimal differentiation (M0-AML) but not in the other cases. Despite the low number of cases, the systematic association between M0-AML, RUNX1 mutations and an excess of pDC is puzzling. Further evaluation in a larger cohort is required to confirm RUNX1 mutations in pDC-AML with minimal differentiation and to investigate whether it represents a proliferation of blasts with macrophage and DC progenitor potential.

Published
2020
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3. Supplementary Tables from Carfilzomib Weekly plus Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Multiple Myeloma (IFM 2012-03): A Phase I Trial

Author

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

Abstract

Supplementary tables 1 to 5

Published
2023

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

Author

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

Abstract

Purpose:Carfilzomib is a novel generation proteasome inhibitor. The Carmysap trial demonstrated that twice-weekly KMP (carfilzomib, melphalan, prednisone) might challenge the MPV (melphalan, prednisone, bortezomib) standard. We sought to study KMP weekly, allowing to increase carfilzomib's dose with maintained efficacy and improved safety profile.Patients and Methods:IFM2012-03, a phase I multicenter study of KMP weekly in elderly patients with newly diagnosed multiple myeloma (eNDMM), aimed to determine the MTD of carfilzomib. Carfilzomib was given intravenously at 36, 45, 56, and 70 mg/m2/day on days 1, 8, 15, and 22 with melphalan and prednisone, for nine 35-day induction cycles, followed by carfilzomib maintenance for 1 year. Three dose-limiting toxicities (DLT) determined MTD at the lower dose.Results:Thirty eNDMMs were treated, 6 per cohort at 36, 45, and 56 mg/m2 and 12 at 70 mg/m². There was one DLT at 36 mg/m2 (lymphopenia), one at 45 mg/m2 (lysis syndrome), two at 56 mg/m2 (cardiac insufficiency and febrile neutropenia), and two at 70 mg/m2 (vomiting and elevated liver enzymes). The safety profile was acceptable; however, specific attention must be paid to the risk of cardiovascular events, especially for elderly patients. The overall response rate was 93.3%, with 46.6% complete response.Conclusions:The MTD dose of carfilzomib was 70 mg/m2 in this KMP weekly study in eNDMM. Response rates, and especially CR rate, were remarkable in this population, and would benefit from being assessed in a larger-scale study. The IFM2012-03 study demonstrated that the MTD of carfilzomib weekly is 70 mg/m2 in eNDMM, and 56 mg/m2 for patients older than 75 years. Carfilzomib used weekly in combination has a good efficacy and safety profile in eNDMM.

Published
2023

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

Author

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

Abstract

Supplementary Figure 1. Complementary survival curves for the whole cohort (n=30). (A) Event Free Survival (EFR); (B) Time to new treatment (TTNT); (C) Duration of response (DOR). Supplementary Figure 2. Progression Free Survival and Overall Survival according to cytogenetic risk (n=30). (A) PFS according to cytogenetic risk; (B) OS according to cytogenetic risk.

Published
2023

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

Author

Murielle Roussel, Valérie Lauwers-Cances, Margaret Macro, Xavier Leleu, Bruno Royer, Cyrille Hulin, Lionel Karlin, Aurore Perrot, Cyrille Touzeau, Marie-Lorraine Chrétien, Sophie Rigaudeau, Mamoun Dib, Emmanuelle Nicolas-Virelizier, Martine Escoffre-Barbe, Karim Belhadj, Clara Mariette, Anne-Marie Stoppa, Carla Araujo, Chantal Doyen, Jean Fontan, Brigitte Kolb, Laurent Garderet, Sabine Brechignac, Jean-Valère Malfuson, Arnaud Jaccard, Pascal Lenain, Cécile Borel, Benjamin Hebraud, Omar Benbrahim, Véronique Dorvaux, Salomon Manier, Karine Augeul-Meunier, Marie-Christiane Vekemans, Edouard Randriamalala, Driss Chaoui, Jo Caers, Carine Chaleteix, Lofti Benboubker, Laure Vincent, Sylvie Glaisner, Patricia Zunic, Borhane Slama, Jean-Richard Eveillard, Catherine Humbrecht-Kraut, Véronique Morel, Philippe Mineur, Jean-Claude Eisenmann, Hélène Demarquette, Valentine Richez, Marguerite Vignon, Denis Caillot, Thierry Facon, Philippe Moreau, Anne-Laurène Colin, Pascale Olivier, Soraya Wuilleme, Hervé Avet-Loiseau, Jill Corre, Michel Attal, UCL - (MGD) Service d'hématologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne

Subjects
Bortezomib, Antineoplastic Combined Chemotherapy Protocols, Immunology, Humans, Cell Biology, Hematology, Multiple Myeloma, Melphalan, Transplantation, Autologous, Biochemistry
Abstract

High-dose melphalan (HDM) and transplantation are recommended for eligible patients with multiple myeloma. No other conditioning regimen has proven to be more effective and/or safer. We previously reported in a phase 2 study that bortezomib can safely and effectively be combined with HDM (Bor-HDM), with a 32% complete response (CR) rate after transplantation. These data supported a randomized phase 3 trial. Randomization was stratified according to risk and response to induction: 300 patients were enrolled, and 154 were allocated to the experimental arm (ie, arm A) with bortezomib (1 mg/m2 intravenously [IV]) on days −6, –3, +1, and +4 and melphalan (200 mg/m2 IV) on day –2. The control arm (ie, arm B) consisted of HDM alone (200 mg/m2 IV). There were no differences in stringent CR + CR rates at day 60 posttransplant (primary end point): 22.1% in arm A vs 20.5% in arm B (P = .844). There were also no differences in undetectable minimum residual disease rates: 41.3% vs 39.4% (P = .864). Median progression-free survival was 34.0 months for arm A vs 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P = .244). The estimated 3-year overall survival was 89.5% in both arms (hazard ratio, 1.28; 95% CI, 0.62-2.64; P = .374). Sixty-nine serious adverse events occurred in 18.7% of Bor-HDM–treated patients (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at www.clinicaltrials.gov as #NCT02197221.

Published
2022

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

Author

Charles Dumontet, Delphine Demangel, Perrine Galia, Lionel Karlin, Laurent Roche, Mathieu Fauvernier, Camille Golfier, Marie‐Charlotte Laude, Xavier Leleu, Philippe Rodon, Murielle Roussel, Isabelle Azaïs, Chantal Doyen, Borhane Slama, Salomon Manier, Olivier Decaux, Maroulio Pertesi, Marie Beaumont, Denis Caillot, Eileen M. Boyle, Manuel Cliquennois, Pascale Cony‐Makhoul, Anne‐Violaine Doncker, Véronique Dorvaux, Marie Odile Petillon, Jean Fontan, Bénédicte Hivert, Isabelle Leduc, Cécile Leyronnas, Margaret Macro, Michel Maigre, Clara Mariette, Philippe Mineur, Sophie Rigaudeau, Bruno Royer, Laure Vincent, James Mckay, Emeline Perrial, Laurent Garderet, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Fédération Française pour la Recherche contre le Myélome et les Gammapathies (FFRMG) Institut National Du Cancer, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie

Subjects
Chromosome Aberrations, MESH: Humans, Paraproteinemias, MESH: Multiple Myeloma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Prognosis, Monoclonal Gammopathy of Undetermined Significance, MESH: Prognosis, MESH: Paraproteinemias, MESH: Child, MESH: Monoclonal Gammopathy of Undetermined Significance, Humans, MESH: Chromosome Aberrations, Child, Multiple Myeloma
Abstract

International audience; Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full-blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow-up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.

Published
2023

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

Author

Sophie Cereja, Damien Roos-Weil, Laurent Voillat, Marie-Odile Petillon, Véronique Dorvaux, Marie-Lorraine Chretien, Nathalie Meuleman, Hervé Avet-Loiseau, Arthur Bobin, Olivier Fitoussi, Carla Araujo, Murielle Roussel, Eric Voog, Frédérique Kuhnowski, Intergroupe Francophone du Myelome Multiple, Jean Claude Eisenmann, Mourad Tiab, Catherine Humbrecht-Kraut, Thierry Facon, Jean-Valère Malfuson, Brigitte Kolb, Karim Belhadj-Merzoug, Philippe Rodon, Pascal Bourquard, Lionel Karlin, Olivier Decaux, Maeva Kyheng, Valentine Richez, Sophie Rigaudeau, Jamile Frayfer, Xavier Leleu, Philippe Moreau, Arnaud Jaccard, Alain Duhamel, Aurore Perrot, Pascal Lenain, Cyrille Hulin, Cécile Gruchet-Merouze, Jean Fontan, Anna Schmitt, Stéphanie Guidez, Fritz Offner, INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Limoges, Hôpital Henri Mondor, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Bergonié [Bordeaux], UNICANCER, Institut Curie [Paris], CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], Amgen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Université de Poitiers, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Oncology, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], MEDLINE, Antineoplastic Agents, Newly diagnosed, Maintenance Chemotherapy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, business.industry, Hematology, medicine.disease, Carfilzomib, Progression-Free Survival, 3. Good health, chemistry, 030220 oncology & carcinogenesis, Multiple Myeloma, business, Oligopeptides
Abstract

International audience

Published
2022

9. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis

Author

Kastritis E., Palladini G., Minnema M. C., Wechalekar A. D., Jaccard A., Lee H. C., Sanchorawala V., Gibbs S., Mollee P., Venner C. P., Lu J., Schonland S., Gatt M. E., Suzuki K., Kim K., Cibeira M. T., Beksac M., Libby E., Valent J., Hungria V., Wong S. W., Rosenzweig M., Bumma N., Huart A., Dimopoulos M. A., Bhutani D., Waxman A. J., Goodman S. A., Zonder J. A., Lam S., Song K., Hansen T., Manier S., Roeloffzen W., Jamroziak K., Kwok F., Shimazaki C., Kim J. -S., Crusoe E., Ahmadi T., Tran N., Qin X., Vasey S. Y., Tromp B., Schecter J. M., Weiss B. M., Zhuang S. H., Vermeulen J., Merlini G., Comenzo R. L., Bradley Augustson, Fiona Kwok, Peter Mollee, Simon Gibbs, Chantal Doyen, Greet Bries, Isabelle Vande Broek, Ka Lung Wu, Koen Theunissen, Koen Van Eygen, Michel Delforge, Nathalie Meuleman, Philip Vlummens, Angelo Maiolino, Breno Moreno de Gusmão, Carlos Eduardo Miguel, Edvan Crusoe, Fernanda Moura, Fernanda Seguro, Jandey Bigonha, Juliane Musacchio, Karla Zanella, Laura Garcia, Marcelo Eduardo Zanella Capra, Reijane Alves de Assis, Rosane Bittencourt, Vania Hungria, Walter Braga, Wolney Barreto, Christopher Venner, Donna Reece, Emilie Lemieux-Blanchard, Kevin Song, Michael Sebag, Selay Lam, Victor Zepeda, Haitao Zhang, Jianda Hu, Jin Lu, Juan Li, Songfu Jiang, Ting Niu, Wenming Chen, Xiaonong Chen, Zhen Cai, Zhou Fude, Maja Oelholm Vase, Morten Salomo, Niels Abildgaard, Alain Fuzibet, Anne-Marie Stoppa, Arnaud Jaccard, Bertrand Arnulf, Bruno Moulin, Bruno Royer, David Ghez, Denis Caillot, Dominique Chauveau, Franck Bridoux, Lauriane Clement-Filliatre, Lionel Karlin, Lotfi Benboubker, Mamoun Dib, Margaret Macro, Mohamad Mohty, Olivier Decaux, Olivier Hermine, Olivier Tournilhac, Philippe Moreau, Salomon Manier, Sylvain Choquet, Véronique Dorvaux, Alexander Carpinteiro, Axel Nogai, Britta Besemer, Christoph Roellig, Roland Fenk, Stefan Knop, Stefan Schönland, Timon Hansen, Argiris Symeonidis, Efstathios Kastritis, Gabor Mikala, Tamás Masszi, Zsolt Nagy, Celia Suriu, Hila Magen, Iuliana Vaxman, Lev Shvidel, Meir Preis, Moshe Gatt, Noa Lavi, Osnat Jarchowsky, Tamar Tadmor, Yael Cohen, Angelo Vacca, Giovanni Palladini, Mario Boccadoro, Maurizio Martelli, Maurizio Musso, Michele Cavo, Chihiro Shimazaki, Hiroyuki Takamatsu, Kazutaka Sunami, Kenshi Suzuki, Nagaaki Katoh, Shinsuke Iida, Takayuki Ikezoe, Tomoaki Fujisaki, Yuta Katayama, Chang Ki Min, Ho-Jin Shin, Jin Seok Kim, Jung Yong Hong, Ki Hyun Kim, Sung-Soo Yoon, Aline Ramirez, Alvaro Cabrera, Christian Ramos, David Gomez Almaguer, Deborah Martinez, Guillermo Ruiz, Helen Dayani Caballero, Juan Antonio Flores Jimenez, Annemiek Broijl, Laurens Nieuwenhuizen, Monique Minnema, Paula Ypma, Wilfried Roeloffzen, Dominik Dytfeld, Grzegorz Charlinski, Grzegorz Helbig, Krzysztof Jamroziak, Sebastian Grosicki, Wieslaw Jedrzejczak, Albert Oriol Rocafiguera, Elham Askari, Fernando Escalante Barrigon, Isabel Krsnik Castello, Javier De la Rubia Comos, Jesus Martin Sanchez, Joaquin Martinez Lopez, Jose Angel Hernandez Rivas, Luis Felipe Casado Montero, Maria Jesus Blanchard Rodriguez, Maria Teresa Cibeira Lopez, Maria Victoria Mateos Manteca, Marta Sonia Gonzalez Perez, Mercedes Gironella Mesa, Rafael Rios Tamayo, Ramon Lecumberri Villamediana, Ricarda Garcia Sanchez, Sunil Lakhwani, Yolanda Gonzalez, Hareth Nahi, Kristina Carlsson, Markus Hansson, Ulf-Henrik Mellqvist, Ali Unal, Burhan Ferhanoglu, Hayri Ozsan, Levent Undar, Mehmet Turgut, Mehmet Yilmaz, Meral Beksac, Muhlis Cem Ar, Muzaffer Demir, Sevgi Besisik, Ashutosh Wechalekar, Jamie Cavenagh, Jim Cavet, Mark Cook, Rachel Hall, Adam Waxman, Anuj Mahindra, Cesar Rodriguez Valdes, Christine Ye, Craig Reeder, Daphne Friedman, David Siegel, Divaya Bhutani, Edward Libby, Eva Medvedova, Frank Passero, Giada Bianchi, Giampaolo Talamo, Guido Tricot, Hans Lee, Heather Landau, Jan Moreb, Jason Valent, Jeffrey Matous, Jeffrey A Zonder, Jesus Berdeja, Jonathan Kaufman, Keith Stockerl-Goldstein, Keren Osman, Ketan Doshi, Kevin Barton, Larry Anderson, Manisha Bhutani, Mehmet Kocoglu, Michael Rosenzweig, Michael Schuster, Michaela Liedtke, Morie Gertz, Naresh Bumma, Natalie Callander, Raymond Comenzo, Robert Vescio, Roger Pearse, Sandy W Wong, Stacey A Goodman, Stefano Tarantolo, Taimur Sher, Tibor Kovacsovics, Tomer Mark, Vaishali Sanchorawala, William Bensinger, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Kastritis E., Palladini G., Minnema M.C., Wechalekar A.D., Jaccard A., Lee H.C., Sanchorawala V., Gibbs S., Mollee P., Venner C.P., Lu J., Schonland S., Gatt M.E., Suzuki K., Kim K., Cibeira M.T., Beksac M., Libby E., Valent J., Hungria V., Wong S.W., Rosenzweig M., Bumma N., Huart A., Dimopoulos M.A., Bhutani D., Waxman A.J., Goodman S.A., Zonder J.A., Lam S., Song K., Hansen T., Manier S., Roeloffzen W., Jamroziak K., Kwok F., Shimazaki C., Kim J.-S., Crusoe E., Ahmadi T., Tran N., Qin X., Vasey S.Y., Tromp B., Schecter J.M., Weiss B.M., Zhuang S.H., Vermeulen J., Merlini G., and Comenzo R.L., Bradley Augustson, Fiona Kwok, Peter Mollee, Simon Gibbs, Chantal Doyen, Greet Bries, Isabelle Vande Broek, Ka Lung Wu, Koen Theunissen, Koen Van Eygen, Michel Delforge, Nathalie Meuleman, Philip Vlummens, Angelo Maiolino, Breno Moreno de Gusmão, Carlos Eduardo Miguel, Edvan Crusoe, Fernanda Moura, Fernanda Seguro, Jandey Bigonha, Juliane Musacchio, Karla Zanella, Laura Garcia, Marcelo Eduardo Zanella Capra, Reijane Alves de Assis, Rosane Bittencourt, Vania Hungria, Walter Braga, Wolney Barreto, Christopher Venner, Donna Reece, Emilie Lemieux-Blanchard, Kevin Song, Michael Sebag, Selay Lam, Victor Zepeda, Haitao Zhang, Jianda Hu, Jin Lu, Juan Li, Songfu Jiang, Ting Niu, Wenming Chen, Xiaonong Chen, Zhen Cai, Zhou Fude, Maja Oelholm Vase, Morten Salomo, Niels Abildgaard, Alain Fuzibet, Anne-Marie Stoppa, Arnaud Jaccard, Bertrand Arnulf, Bruno Moulin, Bruno Royer, David Ghez, Denis Caillot, Dominique Chauveau, Franck Bridoux, Lauriane Clement-Filliatre, Lionel Karlin, Lotfi Benboubker, Mamoun Dib, Margaret Macro, Mohamad Mohty, Olivier Decaux, Olivier Hermine, Olivier Tournilhac, Philippe Moreau, Salomon Manier, Sylvain Choquet, Véronique Dorvaux, Alexander Carpinteiro, Axel Nogai, Britta Besemer, Christoph Roellig, Roland Fenk, Stefan Knop, Stefan Schönland, Timon Hansen, Argiris Symeonidis, Efstathios Kastritis, Gabor Mikala, Tamás Masszi, Zsolt Nagy, Celia Suriu, Hila Magen, Iuliana Vaxman, Lev Shvidel, Meir Preis, Moshe Gatt, Noa Lavi, Osnat Jarchowsky, Tamar Tadmor, Yael Cohen, Angelo Vacca, Giovanni Palladini, Mario Boccadoro, Maurizio Martelli, Maurizio Musso, Michele Cavo, Chihiro Shimazaki, Hiroyuki Takamatsu, Kazutaka Sunami, Kenshi Suzuki, Nagaaki Katoh, Shinsuke Iida, Takayuki Ikezoe, Tomoaki Fujisaki, Yuta Katayama, Chang Ki Min, Ho-Jin Shin, Jin Seok Kim, Jung Yong Hong, Ki Hyun Kim, Sung-Soo Yoon, Aline Ramirez, Alvaro Cabrera, Christian Ramos, David Gomez Almaguer, Deborah Martinez, Guillermo Ruiz, Helen Dayani Caballero, Juan Antonio Flores Jimenez, Annemiek Broijl, Laurens Nieuwenhuizen, Monique Minnema, Paula Ypma, Wilfried Roeloffzen, Dominik Dytfeld, Grzegorz Charlinski, Grzegorz Helbig, Krzysztof Jamroziak, Sebastian Grosicki, Wieslaw Jedrzejczak, Albert Oriol Rocafiguera, Elham Askari, Fernando Escalante Barrigon, Isabel Krsnik Castello, Javier De la Rubia Comos, Jesus Martin Sanchez, Joaquin Martinez Lopez, Jose Angel Hernandez Rivas, Luis Felipe Casado Montero, Maria Jesus Blanchard Rodriguez, Maria Teresa Cibeira Lopez, Maria Victoria Mateos Manteca, Marta Sonia Gonzalez Perez, Mercedes Gironella Mesa, Rafael Rios Tamayo, Ramon Lecumberri Villamediana, Ricarda Garcia Sanchez, Sunil Lakhwani, Yolanda Gonzalez, Hareth Nahi, Kristina Carlsson, Markus Hansson, Ulf-Henrik Mellqvist, Ali Unal, Burhan Ferhanoglu, Hayri Ozsan, Levent Undar, Mehmet Turgut, Mehmet Yilmaz, Meral Beksac, Muhlis Cem Ar, Muzaffer Demir, Sevgi Besisik, Ashutosh Wechalekar, Jamie Cavenagh, Jim Cavet, Mark Cook, Rachel Hall, Adam Waxman, Anuj Mahindra, Cesar Rodriguez Valdes, Christine Ye, Craig Reeder, Daphne Friedman, David Siegel, Divaya Bhutani, Edward Libby, Eva Medvedova, Frank Passero, Giada Bianchi, Giampaolo Talamo, Guido Tricot, Hans Lee, Heather Landau, Jan Moreb, Jason Valent, Jeffrey Matous, Jeffrey A Zonder, Jesus Berdeja, Jonathan Kaufman, Keith Stockerl-Goldstein, Keren Osman, Ketan Doshi, Kevin Barton, Larry Anderson, Manisha Bhutani, Mehmet Kocoglu, Michael Rosenzweig, Michael Schuster, Michaela Liedtke, Morie Gertz, Naresh Bumma, Natalie Callander, Raymond Comenzo, Robert Vescio, Roger Pearse, Sandy W Wong, Stacey A Goodman, Stefano Tarantolo, Taimur Sher, Tibor Kovacsovics, Tomer Mark, Vaishali Sanchorawala, William Bensinger

Subjects
Male, Treatment outcome, Immunoglobulin Light-chain Amyloidosis/drug therapy, CD38, Dexamethasone, Cyclophosphamide/administration & dosage, Bortezomib, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, CRITERIA, Immunoglobulin Light-chain Amyloidosis, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, biology, Amyloidosis, Antibodies, Monoclonal, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Middle Aged, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Antibody, Human, Adult, Dexamethasone/administration & dosage, ANTIBODY DARATUMUMAB, Immunoglobulin light chain, DIAGNOSIS, Antibodies, Monoclonal/administration & dosage, Disease-Free Survival, 03 medical and health sciences, Humans, Cyclophosphamide, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, Antineoplastic Combined Chemotherapy Protocols/adverse effects, AL AMYLOIDOSIS, Daratumumab, Amyloid fibril, medicine.disease, Molecular biology, Immunoglobulin Light-chain Amyloidosi, biology.protein, Bortezomib/administration & dosage, business, 030215 immunology
Abstract

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease.We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response.A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy.Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).

Published
2021

10. A prospective phase 2 trial of daratumumab in patients with previously treated systemic light-chain amyloidosis

Author

Bertrand Arnulf, Aurore Perrot, Bruno Royer, Laurent Frenzel, David Lavergne, Frank Bridoux, Sylvie Chevret, Fabien Le Bras, Cyrille Touzeau, Giampaolo Merlini, Véronique Dorvaux, Murielle Roussel, Eileen M Boyle, Anne-Marie Stoppa, Margaret Macro, Arnaud Jaccard, Lionel Karlin, Giovanni Palladini, Antoine Huart, and Pierre Morel

Subjects
medicine.medical_specialty, business.industry, Amyloidosis, Immunology, Daratumumab, Phases of clinical research, Cell Biology, Hematology, medicine.disease, Biochemistry, Gastroenterology, Clinical trial, Interquartile range, Internal medicine, Severity of illness, medicine, Adverse effect, business, Multiple myeloma
Abstract

Daratumumab is a human monoclonal antibody targeting CD38, an antigen uniformly expressed by plasma cells in multiple myeloma and light-chain amyloidosis (AL). We report the results of a prospective multicenter phase 2 study of daratumumab monotherapy in AL (NCT02816476). Forty previously treated AL patients with a difference between involved and uninvolved free light chains (dFLC) >50 mg/L were included in 15 centers between September of 2016 and April of 2018. Patients received 6 28-day cycles of IV daratumumab, every week for cycles 1 and 2 and every 2 weeks for cycles 3 through 6. Median age was 69 years (range, 45-83). Twenty-six patients had ≥2 organs involved, with heart in 24 and kidney in 26. Median time from diagnosis to enrollment was 23 months (interquartile range, 4-122), with a median of 3 prior therapies (range, 1-5). At data cutoff (September of 2019), all patients discontinued therapy; 33 received the planned 6 cycles. Overall, 22 patients had hematological response, and 19 patients (47.5%) achieved very good partial response (dFLC

Published
2020

11. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Author

Xavier Cahu, Maxime Desmarets, Thibaut Leguay, Philippe Saas, Victoria Raggueneau, Delphine Binda, Maria Alessandra Rosenthal, Chrystelle Vidal, Olivier Adotevi, Fanny Angelot-Delettre, Françoise Solly, Anne-Cécile Galoisy, Alice Garnier, Sylvie Daliphard, Estelle Guérin, Marie-Pierre Gourin, Karim Maloum, Véronique Harrivel, Edouard Cornet, Felipe Suarez, Jacques Vargaftig, Fabrice Jardin, Caroline Mayeur-Rousse, Sylvain Thepot, Maïder Pagadoy, Thorsten Braun, Bernard Drenou, Yuriy Drebit, Marc Maynadié, Caroline Basle, Zehaira Benseddik, Frédéric Féger, Jean Feuillard, Christian Recher, Etienne Lengliné, Catherine Cordonnier, Rémi Letestu, Mathieu Puyade, Isabelle Arnoux, Remy Gressin, Nathalie Contentin, Jerome Tamburini, Pascale Saussoy, Mary Callanan, Elodie Dindinaud, Pierre-Simon Rohrlich, Julien Guy, Hind Bennani, Tony Petrella, Vincent Foissaud, Johann Rose, Natacha Maillard, Lucile Baseggio, Magali Le Garff-Tavernier, Vincent Barlogis, Denis Guyotat, Yohan Desbrosses, Caroline Bonmati, Damien Roos-Weil, Michel Ticchioni, Sandrine Puyraimond, Norbert Vey, Adriana Plesa, Blandine Guffroy, Daniel Lusina, Bérengère Gruson, Anne Roggy, Véronique Salaun, Eric Deconinck, Jean-Yves Cahn, Nathalie Jacques, Caroline Bret, Florian Renosi, Marie-Christine Béné, Alice Eischen, Stefan Wickenhauser, Benjamin Papoular, Francine Garnache-Ottou, François-Xavier Gros, Vahid Asnafi, Celia Salanoubat, Blandine Bénet, Elisabeth Macintyre, Lou Soret, Orianne Wagner-Ballon, Mohamad Mohty, Elsa Bera, Nicolas Freynet, Ludovic Lhermitte, Franck Trimoreau, Claude Preudhomme, Christophe Roumier, Sébastien Maury, Sabrina Bouyer, Eve Poret, Mikael Roussel, Romaric Lacroix, Christine Arnoulet, Françoise Schillinger, Patricia Okamba, Christine Lefebvre, Didier Blaise, Nicolas Lechevalier, Sabine Brechignac, Christophe Ferrand, Estelle Seilles, Richard Veyrat-Masson, Giorgia Battipaglia, Denis Caillot, Véronique Latger-Cannard, Bruno Quesnel, Didier Bouscary, Sophie Brun, Agathe Debliquis, Marie Loosveld, Franck Geneviève, Carinne Lafon, Lydia Campos, Thierry Fest, Ouda Ghoual, Marie-Christine Jacob, Pierre Peterlin, Valérie Bardet, Anne Arnaud, Véronique Dorvaux, Sabeha Biichle, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], 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), Lipides - Nutrition - Cancer [Dijon - U1231] (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, 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 [2016-2019] (UGA [2016-2019]), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), European Project: IC18CT980373, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), 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]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), 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 ), 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), UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de biologie hématologique, Garnache-Ottou, F., Vidal, C., Biichle, S., Renosi, F., Poret, E., Pagadoy, M., Desmarets, M., Roggy, A., Seilles, E., Soret, L., Schillinger, F., Puyraimond, S., Petrella, T., Preudhomme, C., Roumier, C., Macintyre, E. A., Harrivel, V., Desbrosses, Y., Gruson, B., Genevieve, F., Thepot, S., Drebit, Y., Leguay, T., Gros, F. -X., Lechevalier, N., Saussoy, P., Salaun, V., Cornet, E., Benseddik, Z., Veyrat-Masson, R., Wagner-Ballon, O., Salanoubat, C., Maynadie, M., Guy, J., Caillot, D., Jacob, M. -C., Cahn, J. -Y., Gressin, R., Rose, J., Quesnel, B., Guerin, E., Trimoreau, F., Feuillard, J., Gourin, M. -P., Plesa, A., Baseggio, L., Arnoux, I., Vey, N., Blaise, D., Lacroix, R., Arnoulet, C., Benet, B., Dorvaux, V., Bret, C., Drenou, B., Debliquis, A., Latger-Cannard, V., Bonmati, C., Bene, M. -C., Peterlin, P., Ticchioni, M., Rohrlich, P. -S., Arnaud, A., Wickenhauser, S., Bardet, V., Brechignac, S., Papoular, B., Raggueneau, V., Vargaftig, J., Letestu, R., Lusina, D., Braun, T., Foissaud, V., Tamburini, J., Bennani, H., Freynet, N., Cordonnier, C., Le Garff-Tavernier, M., Jacques, N., Maloum, K., Roos-Weil, D., Bouscary, D., Asnafi, V., Lhermitte, L., Suarez, F., Lengline, E., Feger, F., Battipaglia, G., Mohty, M., Bouyer, S., Ghoual, O., Dindinaud, E., Basle, C., Puyade, M., Lafon, C., Fest, T., Roussel, M., Cahu, X., Bera, E., Daliphard, S., Jardin, F., Campos, L., Solly, F., Guyotat, D., Galoisy, A. -C., Eischen, A., Mayeur-Rousse, C., Guffroy, B., Recher, C., Loosveld, M., Garnier, A., Barlogis, V., Rosenthal, M. A., Brun, S., Contentin, N., Maury, S., Callanan, M., Lefebvre, C., Maillard, N., Okamba, P., Ferrand, C., Adotevi, O., Saas, P., Angelot-Delettre, F., Binda, D., and Deconinck, E.

Subjects
Oncology, Vincristine, medicine.medical_specialty, Myeloid, Cyclophosphamide, Clinical Trials and Observations, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Plasmacytoid dendritic cell, Immunophenotyping, Clonal Evolution, 03 medical and health sciences, 0302 clinical medicine, Bone Marrow, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Neoplasm Metastasis, Neoplasm Staging, 030304 developmental biology, Chromosome Aberrations, 0303 health sciences, Leukemia, business.industry, Hematopoietic Stem Cell Transplantation, Disease Management, Myeloid leukemia, Dendritic Cells, Hematology, Prognosis, medicine.disease, Blood Cell Count, 3. Good health, Transplantation, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Acute Disease, business, Biomarkers, medicine.drug
Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

Published
2019

12. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life-experience of the French Network

Author

Laurence, Schenone, Caroline, Houillier, Marie Laure, Tanguy, Sylvain, Choquet, Kossi, Agbetiafa, Hervé, Ghesquières, Gandhi, Damaj, Anna, Schmitt, Krimo, Bouabdallah, Guido, Ahle, Remy, Gressin, Jérôme, Cornillon, Roch, Houot, Jean-Pierre, Marolleau, Luc-Matthieu, Fornecker, Olivier, Chinot, Frédéric, Peyrade, Reda, Bouabdallah, Cécile, Moluçon-Chabrot, Emmanuel, Gyan, Adrien, Chauchet, Olivier, Casasnovas, Lucie, Oberic, Vincent, Delwail, Julie, Abraham, Virginie, Roland, Agathe, Waultier-Rascalou, Lise, Willems, Franck, Morschhauser, Michel, Fabbro, Renata, Ursu, Catherine, Thieblemont, Fabrice, Jardin, Adrian, Tempescul, Denis, Malaise, Valérie, Touitou, Lucia, Nichelli, Magali, Le Garff-Tavernier, Aurélie, Plessier, Philippe, Bourget, Caroline, Bonmati, Sophie, Wantz-Mézières, Quentin, Giordan, Véronique, Dorvaux, Cyril, Charron, Waliyde, Jabeur, Khê, Hoang-Xuan, Luc, Taillandier, Carole, Soussain, and Thomas, Gastinne

Subjects
Central Nervous System, Lymphoma, Hematopoietic Stem Cell Transplantation, Carmustine, Transplantation, Autologous, Central Nervous System Neoplasms, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Humans, Prospective Studies, Neoplasm Recurrence, Local, Busulfan, Cyclophosphamide, Thiotepa, Etoposide
Abstract

We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.

Published
2021

13. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study

Author

Andrew Lister, Maria Gomes da Silva, John F. Seymour, Harald Zeuner, Jonathan Farhi, John Catalano, Véronique Dorvaux, Sirpa Leppä, David Simpson, Loic Ysebaert, Steven Le Gouill, David Belada, Anne Sonet, Emmanuel Bachy, Pauline Brice, Luc Xerri, Tanin Intragumtornchai, Lars Møller Pedersen, Anne Vekhoff, Sylvie Glaisner, Jane Estell, Gilles Salles, Alejandro Martín, Hervé Tilly, Olivier Casasnovas, François Lemonnier, Fritz Offner, Jean Gabarre, Armando López-Guillermo, Gustavo Milone, Pierre Feugier, Department of Oncology, HUS Comprehensive Cancer Center, and University of Helsinki

Subjects
Oncology, Male, Cancer Research, Time Factors, Follicular lymphoma, THERAPY, 0302 clinical medicine, Antineoplastic Agents, Immunological, Prednisone, CYCLOPHOSPHAMIDE, Lymphoma and Myeloma, Lymphoma, Follicular, R-CVP, Aged, 80 and over, Middle Aged, CHEMOTHERAPY, Progression-Free Survival, 3. Good health, 030220 oncology & carcinogenesis, Disease Progression, Rituximab, Female, TRIAL, medicine.drug, Adult, PREDNISONE, medicine.medical_specialty, Vincristine, Cyclophosphamide, 3122 Cancers, 03 medical and health sciences, Young Adult, Internal medicine, RAPID COMMUNICATIONS, medicine, Humans, Progression-free survival, NON-HODGKINS-LYMPHOMA, VINCRISTINE, Watchful Waiting, Aged, business.industry, medicine.disease, PHASE-III, Lymphoma, Clinical trial, business, RESPONSE DURATION, 030215 immunology
Abstract

PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582 ) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (> 18 years of age) with previously untreated high–tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m2, once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P < .001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.

Published
2019

14. Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial

Author

Norbert Ifrah, Hacene Zerazhi, Pierre-Yves Dumas, Norbert Vey, Isabelle Luquet, Denis Caillot, Marie-Christine Béné, Célestine Simand, Marie-Pierre Ledoux, Véronique Dorvaux, Yosr Hicheri, Anne Banos, Maria Pilar Gallego Hernanz, Chantal Himberlin, Odile Blanchet, Eric Delabesse, Catherine Humbrecht, Pascal Turlure, Arnaud Pigneux, Eric Jourdan, Jacques Delaunay, Didier Bouscary, Emmanuelle Tavernier, Christian Recher, Gaelle Guillerm, Mathilde Hunault-Berger, Romain Guieze, Martin Carre, Anne Bouvier, Jean-Pierre Marolleau, Claude Eric Bulabois, Pascale Cornillet-Lefebvre, Mario Ojeda-Uribe, Marc Bernard, Magda Alexis, Jean-François Hamel, Etienne Daguindau, Pierre Peterlin, Gabrielle Roth Guepin, Emmanuel Gyan, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital privé du Confluent [Nantes], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France., Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Reims (CHU Reims), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang [Angers], CHU Pontchaillou [Rennes], Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Henri Duffaut (Avignon), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Ressources Biologiques [CHU Angers], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Oncology, Adult, Male, Risk, medicine.medical_specialty, NPM1, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Phases of clinical research, Gene mutation, Disease-Free Survival, Cytogenetics, Young Adult, Internal medicine, hemic and lymphatic diseases, CEBPA, Medicine, Cluster Analysis, Humans, Chemotherapy, business.industry, Gene Expression Regulation, Leukemic, Gene Expression Profiling, Remission Induction, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, General Medicine, Middle Aged, Prognosis, Gemtuzumab, Transplantation, Leukemia, Myeloid, Acute, Karyotyping, Cytogenetic Analysis, Mutation, Female, business
Abstract

International audience; In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m(2) of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (

Published
2021

15. Long-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for chronic myeloid leukaemia: results from the French SPIRIT phase III randomised trial

Author

Véronique Dorvaux, Marc Delord, Marc Muller, Melanie Mercier, Hacene Zerazhi, Jacques Chapiro, Eric Jourdan, Laurence Legros, Françoise Rigal-Huguet, Iona Vaida, François Guilhot, Alberto Santagostino, Claude Preudhomme, Joelle Guilhot, Valérie Coiteux, Jean-Michel Miclea, Jean-Jacques Kiladjian, Emmanuel Gyan, Aude Charbonnier, Amélie Penot, Eric Deconinck, Franck E. Nicolini, Gabriel Etienne, Hyacinthe Johnson-Ansah, Jean-Claude Chomel, Kamel Ghomari, Nathalie Cambier, Delphine Lebon, Viviane Dubruille, Sylvie Glaisner, Philippe Rousselot, Loïc Fouillard, Alain Delmer, Bertrand Joly, Pascal Lenain, Claude-Eric Bulabois, Martine Escoffre Barbe, Christian Berthou, Isabelle Plantier, Delphine Rea, Marc G. Berger, Magda Alexis, Francois-Xavier Mahon, Pascale Cony-Makhoul, Ludovic Lhermitte, Lydia Roy, Jean-Michel Cayuela, Denis Caillot, Anne Vekhoff, Martine Gardembas, Bertrand Pollet, Agnès-Paule Guerci-Bresler, Yazid Arkam, Hervé Maisonneuve, Frédéric Maloisel, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne (UCA)

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Chronic myeloid leukaemia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Interferon, Internal medicine, Medicine, Adverse effect, ComputingMilieux_MISCELLANEOUS, business.industry, Imatinib, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Major Molecular Response, Pegylated interferon alpha 2a, Toxicity, Cytarabine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

The STI571 prospective randomised trial (SPIRIT) French trial is a four-arm study comparing imatinib (IM) 400 mg versus IM 600 mg, IM 400 mg + cytarabine (AraC), and IM 400 mg + pegylated interferon alpha2a (PegIFN-α2a) for the front-line treatment of chronic-phase chronic myeloid leukaemia (CML). Long-term analyses included overall and progression-free survival, molecular responses to treatment, and severe adverse events. Starting in 2003, the trial included 787 evaluable patients. The median overall follow-up of the patients was 13.5 years (range 3 months to 16.7 years). Based on intention-to-treat analyses, at 15 years, overall and progression-free survival were similar across arms: 85%, 83%, 80%, and 82% and 84%, 87%, 79%, and 79% for the IM 400 mg (N = 223), IM 600 mg (N = 171), IM 400 mg + AraC (N = 172), and IM 400 mg + PegIFN-α2a (N = 221) arms, respectively. The rate of major molecular response at 12 months and deep molecular response (MR4) over time were significantly higher with the combination IM 400 mg + PegIFN-α2a than with IM 400 mg: p = 0.0001 and p = 0.0035, respectively. Progression to advanced phases and secondary malignancies were the most frequent causes of death. Toxicity was the main reason for stopping AraC or PegIFN-α2a treatment.

Published
2021

16. Bortezomib, thalidomide, and dexamethasone with or without daratumumab for transplantation-eligible patients with newly diagnosed multiple myeloma (CASSIOPEIA): health-related quality of life outcomes of a randomised, open-label, phase 3 trial

Author

Benjamin Hebraud, Pieter Sonneveld, Arnaud Jaccard, Saskia K. Klein, Véronique Dorvaux, Kon Siong Jie, Laurent Frenzel, Borhane Slama, Bruno Royer, Katharine S. Gries, Sonja Zweegman, Annemiek Broijl, Veronique Vanquickelberghe, Mamoun Dib, Carla de Boer, Jianping Wang, John Fastenau, Murielle Roussel, Philippe Moreau, Kamel Laribi, Tobias Kampfenkel, Hematology, and CCA - Cancer Treatment and quality of life

Subjects
Male, medicine.medical_specialty, Visual analogue scale, Population, Dexamethasone, law.invention, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, education, Multiple myeloma, education.field_of_study, business.industry, Daratumumab, Antibodies, Monoclonal, Hematology, medicine.disease, Thalidomide, Transplantation, Clinical trial, 030220 oncology & carcinogenesis, Quality of Life, Female, business, Multiple Myeloma, 030215 immunology, medicine.drug
Abstract

Summary Background In part 1 of the two-part CASSIOPEIA study, treatment before and after autologous haematopoietic stem-cell transplantation (HSCT) with daratumumab plus bortezomib, thalidomide, and dexamethasone (D-VTd) significantly improved rates of stringent complete response and progression-free survival versus bortezomib, thalidomide, and dexamethasone (VTd) in patients with newly diagnosed multiple myeloma. Methods CASSIOPEIA is an ongoing randomised, open-label, active-controlled, parallel-group, phase 3 trial done at 111 academic and community practice centres in Europe. Transplantation-eligible adults with newly diagnosed multiple myeloma were randomly assigned (1:1) to D-VTd or VTd. Treatment consisted of four 28-day cycles of induction therapy before autologous HSCT and two 28-day cycles of consolidation therapy after. In this prespecified secondary analysis, patient-reported outcomes were assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire-core 30-item (EORTC QLQ-C30) and EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaire at baseline, after induction (cycle 4, day 28), and after consolidation (day 100 after autologous HSCT). The analysis was done in all patients in the intention-to-treat population with a baseline and at least one post-baseline patient-reported outcome assessment. The trial is registered at ClinicalTrials.gov ( NCT02541383 ). Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled and randomly assigned D-VTd (n=543) or VTd (n=542). Questionnaire completion rates were high at baseline (511 [94%] of 543 in the D-VTd group vs 510 [94%] of 542 in the VTd group). Compliance rates (calculated from the number of completed surveys as a proportion of the predicted number of participants still on study treatment) were high at post-induction (431 [84%] of 513 vs 405 [80%] of 509) and post-consolidation (414 [90%] of 460 vs 386 [88%] of 438) assessments and were similar between treatment groups. Mean changes in global health status scores from baseline to post-induction were not different between the D-VTd group (3·8 [95% CI 1·6 to 6·0]) and VTd group (2·9 [0·7 to 5·1]; p=0·43), or from baseline to post-consolidation between the two groups (D-VTd group, 9·7 (95% CI 7·4 to 11·9) vs VTd group, 8·7 (6·5 to 11·0; p=0·45). Improvements from baseline in EORTC QLQ-C30 global health status and EQ-5D-5L visual analogue scale scores were observed in post-consolidation scores in both groups. Post-consolidation scores showed significantly greater mean decreases in pain (−23·3 [95% CI −26·6 to −20·0] in the D-VTd group vs −19·7 [−23·0 to −16·3] in the VTd group; p=0·042), significantly smaller reductions in cognitive functioning (−5·0 [−7·6 to −2·4] vs −7·9 [−10·6 to −5·3]; p=0·036), and significantly greater improvements in emotional functioning (13·0 [10·4 to 15·5] vs 9·5 [6·9 to 12·1]; p=0·013) and in constipation (–3·2 [–7·3 to 0·9] vs 1·8 [–2·4 to 6·0]; p=0·025) with D-VTd versus VTd. Between-group differences in change from baseline for all other scales were not significant. Interpretation D-VTd and VTd were associated with on-treatment health-related quality of life improvements from baseline in transplantation-eligible patients with newly diagnosed multiple myeloma. The significantly greater reductions in pain, less deterioration of cognitive functioning, and greater emotional functioning improvements complement the clinical benefits observed with D-VTd versus VTd, and support the addition of daratumumab to standard regimens in patients with newly diagnosed multiple myeloma. Funding Intergroupe Francophone du Myelome, The Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research and Development.

Published
2020

17. Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape

Author

Fabrice Jardin, Elodie Dindinaud, Meyling Cheok, Fanny Angelot-Delettre, Victor Baunin, Caroline Mayeur-Rousse, Victoria Raggueneau, Bernard Drenou, Christophe Ferrand, Patricia Okamba, Johann Rose, Marie-Thérèse Rubio, Etienne Daguindau, Véronique Dorvaux, Loria Zalmaï, Eric Deconinck, Florian Renosi, Claude Preudhomme, Pierre-Julien Viailly, Olivier Adotevi, Christophe Roumier, Michel Tichionni, Francine Garnache-Ottou, Damien Roos-Weil, Sabrina Bouyer, Sabeha Biichle, Sandrine Geffroy, Marie-Agnès Collonge-Rame, Marie Christine Jacob, Tony Petrella, Jean Feuillard, Philippe Saas, Magali Le Garff-Tavernier, Lou Soret, Véronique Salaun, Orianne Wagner-Ballon, Estelle Seilles, Sophie Brun, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Université de Montréal (UdeM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CH La Rochelle, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Henri Mondor, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Limoges, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Strasbourg, Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Le Mans (CH Le Mans), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier de Versailles André Mignot (CHV), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Myeloid, CD34, Chronic myelomonocytic leukemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, Biology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, medicine, Humans, Cell Proliferation, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, hemic and immune systems, Hematology, Dendritic Cells, medicine.disease, 3. Good health, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Phenotype, RUNX1, chemistry, 030220 oncology & carcinogenesis, Mutation, Cancer research, Interleukin-3 receptor, CD5, 030215 immunology
Abstract

Neoplasms involving plasmacytoid dendritic cells (pDC) include blastic pDC neoplasms (BPDCN) and other pDC proliferations, where pDC are associated with myeloid malignancies: most frequently chronic myelomonocytic leukemia (CMML) but also acute myeloid leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDC in pDC-AML, and their link with the CD34+ blasts, monocytes or conventional DC (cDC) associated in the same sample, by phenotypic and molecular analyses (targeted next-generation sequencing, 70 genes). We compared 15 pDCAML at diagnosis with 21 BPDCN and 11 normal pDC from healthy donors. CD45low CD34+ blasts were found in all cases (10-80% of medullar cells), associated with pDC (4-36%), monocytes in 14 cases (1-10%) and cDC (two cases, 4.8-19%). pDC in pDC-AML harbor a clearly different phenotype from BPDCN: CD4+ CD56– in 100% of cases, most frequently CD303+, CD304+ and CD34+; lower expression of cTCL1 and CD123 with isolated lymphoid markers (CD22/CD7/CD5) in some cases, suggesting a prepDC stage. In all cases, pDC, monocytes and cDC are neoplastic since they harbor the same mutations as CD34+ blasts. RUNX1 is the most commonly mutated gene: detected in all AML with minimal differentiation (M0-AML) but not in the other cases. Despite the low number of cases, the systematic association between M0-AML, RUNX1 mutations and an excess of pDC is puzzling. Further evaluation in a larger cohort is required to confirm RUNX1 mutations in pDC-AML with minimal differentiation and to investigate whether it represents a proliferation of blasts with macrophage and DC progenitor potential.

Published
2020

18. Long-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for chronic myeloid leukaemia: results from the French SPIRIT phase III randomised trial

Author

Francois, Guilhot, Françoise, Rigal-Huguet, Joëlle, Guilhot, Agnès-Paule, Guerci-Bresler, Frédéric, Maloisel, Delphine, Rea, Valérie, Coiteux, Martine, Gardembas, Christian, Berthou, Anne, Vekhoff, Eric, Jourdan, Marc, Berger, Loïc, Fouillard, Magda, Alexis, Laurence, Legros, Philippe, Rousselot, Alain, Delmer, Pascal, Lenain, Martine, Escoffre Barbe, Emmanuel, Gyan, Claude-Eric, Bulabois, Viviane, Dubruille, Bertrand, Joly, Bertrand, Pollet, Pascale, Cony-Makhoul, Hyacinthe, Johnson-Ansah, Melanie, Mercier, Denis, Caillot, Aude, Charbonnier, Jean-Jacques, Kiladjian, Jacques, Chapiro, Amélie, Penot, Véronique, Dorvaux, Iona, Vaida, Alberto, Santagostino, Lydia, Roy, Hacene, Zerazhi, Eric, Deconinck, Herve, Maisonneuve, Isabelle, Plantier, Delphine, Lebon, Yazid, Arkam, Nathalie, Cambier, Kamel, Ghomari, Jean-Michel, Miclea, Sylvie, Glaisner, Jean-Michel, Cayuela, Jean-Claude, Chomel, Marc, Muller, Ludovic, Lhermitte, Marc, Delord, Claude, Preudhomme, Gabriel, Etienne, François-Xavier, Mahon, and Franck-Emmanuel, Nicolini

Subjects
Adult, Aged, 80 and over, Male, Dose-Response Relationship, Drug, Cytarabine, Interferon-alpha, Middle Aged, Prognosis, Recombinant Proteins, Polyethylene Glycols, Survival Rate, Young Adult, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Antineoplastic Combined Chemotherapy Protocols, Imatinib Mesylate, Humans, Female, Prospective Studies, Aged, Follow-Up Studies
Abstract

The STI571 prospective randomised trial (SPIRIT) French trial is a four-arm study comparing imatinib (IM) 400 mg versus IM 600 mg, IM 400 mg + cytarabine (AraC), and IM 400 mg + pegylated interferon alpha2a (PegIFN-α2a) for the front-line treatment of chronic-phase chronic myeloid leukaemia (CML). Long-term analyses included overall and progression-free survival, molecular responses to treatment, and severe adverse events. Starting in 2003, the trial included 787 evaluable patients. The median overall follow-up of the patients was 13.5 years (range 3 months to 16.7 years). Based on intention-to-treat analyses, at 15 years, overall and progression-free survival were similar across arms: 85%, 83%, 80%, and 82% and 84%, 87%, 79%, and 79% for the IM 400 mg (N = 223), IM 600 mg (N = 171), IM 400 mg + AraC (N = 172), and IM 400 mg + PegIFN-α2a (N = 221) arms, respectively. The rate of major molecular response at 12 months and deep molecular response (MR4) over time were significantly higher with the combination IM 400 mg + PegIFN-α2a than with IM 400 mg: p = 0.0001 and p = 0.0035, respectively. Progression to advanced phases and secondary malignancies were the most frequent causes of death. Toxicity was the main reason for stopping AraC or PegIFN-α2a treatment.

Published
2020

19. Prospective Evaluation of Magnetic Resonance Imaging and [18F]Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the IFM/DFCI 2009 Trial: Results of the IMAJEM Study

Author

Paul G. Richardson, Hervé Avet-Loiseau, Benoit Dupas, Martine Escoffre-Barbe, Aurore Perrot, Eric Frampas, Caroline Bodet-Milin, Lotfi Benboubker, Michel Attal, Thierry Facon, Gerald Marit, Jean-Richard Eveillard, Florence Caillon, Cyrille Hulin, Véronique Dorvaux, Lionel Karlin, Carine Chaleteix, Denis Caillot, Anne-Marie Stoppa, Brigitte Pegourie, Philippe Moreau, Kamel Laribi, Laurent Garderet, Jean-Michel Nguyen, Nikhil C. Munshi, Kenneth C. Anderson, Aurélie Gaultier, Margaret Macro, and Françoise Kraeber-Bodéré

Subjects
Cancer Research, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Bortezomib, Magnetic resonance imaging, medicine.disease, 3. Good health, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Oncology, Maintenance therapy, 030220 oncology & carcinogenesis, Clinical endpoint, Medicine, Radiology, business, Nuclear medicine, Survival rate, Multiple myeloma, 030215 immunology, medicine.drug, Lenalidomide
Abstract

Purpose Magnetic resonance imaging (MRI) and positron emission tomography–computed tomography (PET-CT) are important imaging techniques in multiple myeloma (MM). We conducted a prospective trial in patients with MM aimed at comparing MRI and PET-CT with respect to the detection of bone lesions at diagnosis and the prognostic value of the techniques. Patients and Methods One hundred thirty-four patients received a combination of lenalidomide, bortezomib, and dexamethasone (RVD) with or without autologous stem-cell transplantation, followed by lenalidomide maintenance. PET-CT and MRI were performed at diagnosis, after three cycles of RVD, and before maintenance therapy. The primary end point was the detection of bone lesions at diagnosis by MRI versus PET-CT. Secondary end points included the prognostic impact of MRI and PET-CT regarding progression-free (PFS) and overall survival (OS). Results At diagnosis, MRI results were positive in 127 of 134 patients (95%), and PET-CT results were positive in 122 of 134 patients (91%; P = .33). Normalization of MRI after three cycles of RVD and before maintenance was not predictive of PFS or OS. PET-CT became normal after three cycles of RVD in 32% of the patients with a positive evaluation at baseline, and PFS was improved in this group (30-month PFS, 78.7% v 56.8%, respectively). PET-CT normalization before maintenance was described in 62% of the patients who were positive at baseline. This was associated with better PFS and OS. Extramedullary disease at diagnosis was an independent prognostic factor for PFS and OS, whereas PET-CT normalization before maintenance was an independent prognostic factor for PFS. Conclusion There is no difference in the detection of bone lesions at diagnosis when comparing PET-CT and MRI. PET-CT is a powerful tool to evaluate the prognosis of de novo myeloma.

Published
2017

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

Author

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

Subjects
Male, Melphalan, Oncology, Cancer Research, medicine.medical_specialty, Maximum Tolerated Dose, Population, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Prednisone, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, cardiovascular diseases, education, Survival rate, neoplasms, Response Evaluation Criteria in Solid Tumors, Multiple myeloma, Aged, Aged, 80 and over, education.field_of_study, Bortezomib, business.industry, Hematopoietic Stem Cell Transplantation, Sciences bio-médicales et agricoles, medicine.disease, Carfilzomib, Survival Rate, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Female, Patient Safety, Multiple Myeloma, business, Oligopeptides, Febrile neutropenia, 030215 immunology, medicine.drug
Abstract

Carfilzomib is a novel generation proteasome inhibitor. The Carmysap trial demonstrated that twice-weekly KMP (carfilzomib, melphalan, prednisone) might challenge the MPV (melphalan, prednisone, bortezomib) standard. We sought to study KMP weekly, allowing to increase carfilzomib's dose with maintained efficacy and improved safety profile., info:eu-repo/semantics/published

Published
2019

21. BAM conditioning before autologous transplantation for lymphoma: a study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

Author

Magda Alexis, Marie-Lorraine Chretien, Nathalie Contentin, Emmanuel Gyan, Sandy Amorim, Emmanuelle Nicolas-Virelizier, Caroline Lejeune, Jacques-Olivier Bay, Chantal Himberlin, Jérôme Cornillon, Régis Peffault de Latour, Gilles Salles, Thomas Cluzeau, Adrien Chauchet, Nicolas Vallet, Mélanie Mercier, Elisabeth Daguenet, Véronique Dorvaux, Anne Huynh, Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de 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), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Léon Bérard [Lyon], Service des maladies du sang, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Mathématiques & Sécurité de l'information (XLIM-MATHIS), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-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 Universitaire de Reims (CHU Reims), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de la Loire Lucien Neuwirth, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Saint-Etienne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], and Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)

Subjects
Adult, Male, Mucositis, Melphalan, Oncology, medicine.medical_specialty, Transplantation Conditioning, Lymphoma, medicine.medical_treatment, Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Autologous transplantation, Busulfan, ComputingMilieux_MISCELLANEOUS, Bone Marrow Transplantation, Retrospective Studies, Chemotherapy, Hematology, Performance status, business.industry, Age Factors, Cytarabine, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Middle Aged, Prognosis, medicine.disease, Survival Analysis, 3. Good health, Regimen, 030220 oncology & carcinogenesis, Multivariate Analysis, Female, France, business, 030215 immunology, medicine.drug
Abstract

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity.

Published
2019

22. 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

23. 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

24. Peritoneal Myeloid Sarcoma in a Patient Treated for a Testicular Seminoma

Author

Marco Campitiello, Eric Chatelain, Francesca Plastino, Nathalie Marcon, Philippe Quétin, Véronique Dorvaux, Nada Eid, Raffaele Longo, and Laurent Hennequin

Subjects
Male, Myeloid, Pathology, medicine.medical_specialty, medicine.medical_treatment, Acute, 03 medical and health sciences, 0302 clinical medicine, Testicular Neoplasms, medicine, Myeloid sarcoma, Humans, Sarcoma, Myeloid, Peritoneal Neoplasms, Chemotherapy, Leukemia, business.industry, Myeloid leukemia, Induction chemotherapy, Sarcoma, General Medicine, Articles, Middle Aged, medicine.disease, Monoblastic Sarcoma, Seminoma, Leukemia, Myeloid, Acute, medicine.anatomical_structure, 030220 oncology & carcinogenesis, business, 030215 immunology
Abstract

Patient: Male, 46 Final Diagnosis: Myeloid sarcoma Symptoms: — Medication: — Clinical Procedure: Laparoscopy • CT scan • Pet-scan Specialty: Oncology Objective: Rare disease Background: Myeloid sarcoma is a rare extramedullary soft tissue neoplasm composed of myeloblastic cells, usually associated to hematologic tumor disorders and a poor prognosis. Its diagnosis is very difficult as radiological images are not specific. Histology and immunohistochemistry are necessary for an accurate diagnosis. Case Report: We report the case of 46-year-old, Caucasian, non-smoker male, treated in 2014 by orchiectomy and systemic chemotherapy for a stage IIB testicular seminoma. Considering the rapid increase of lactate dehydrogenase (LDH) levels without any evident medical reason, a computed tomography/positron emission tomography (CT/PET) scan was performed and revealing a diffuse, nodular, peritoneal tumor infiltration associated with multiple mesenteric and mediastinal adenopathies. Laparoscopy confirmed a diffuse tumor infiltration of the peritoneum. Histology and immunohistochemistry were consisted with the diagnosis of a myeloid monoblastic sarcoma. Cytology of bone marrow documented an monocytic acute myeloid leukemia. The patient started a systemic induction chemotherapy with high dose cytarabine and idarubicin that was complicated by an infectious pneumonia and colitis, and a grade IV thrombocytopenia leading to a brain subdural hemorrhage and quickly to patient’s death. Conclusions: We describe a rare, peritoneal, myeloid sarcoma in a young patient who had been treated by systemic chemo-therapy for testicular seminoma 4 years earlier. The patient was clinically asymptomatic and presented only elevated LDH levels without any evident clinical reason. Considering the persistence of this biochemical abnormality, more investigations were performed leading to a diagnosis of peritoneal myeloid sarcoma associated with monocytic acute myeloid leukemia, probably secondary to the past chemotherapy.

Published
2018

25. A Prospective Phase II of Daratumumab in Previously Treated Systemic Light-Chain (AL) Amyloidosis: Updated Results

Author

Anne-Marie Stoppa, Aurore Perrot, Margaret Macro, Bruno Royer, Giovanni Palladini, Frank Bridoux, Laurent Frenzel, Murielle Roussel, Giampaolo Merlini, Véronique Dorvaux, Salomon Manier, David Lavergne, Antoine Huart, Bertrand Arnulf, Lionel Karlin, Pierre Morel, and Arnaud Jaccard

Subjects
Cancer Research, medicine.medical_specialty, business.industry, Daratumumab, Hematology, medicine.disease, Immunoglobulin light chain, Gastroenterology, Oncology, Internal medicine, Phase (matter), medicine, AL amyloidosis, Previously treated, business
Published
2019

26. An Incidental Finding of Maternal Multiple Myeloma by Non Invasive Prenatal Testing

Author

Joris Vermeesch, Peter Vandenberghe, Sanae Finge, Véronique Dorvaux, Eric Legius, Marion Imbert-Bouteille, Pascal Bourquard, Vincent Gatinois, Lucille Altounian, Jean Chiesa, Jean-Baptiste Gaillard, E Mousty, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and University Hospitals Leuven [Leuven]

Subjects
Adult, 0301 basic medicine, Oncology, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 03 medical and health sciences, 0302 clinical medicine, Text mining, Pregnancy, Internal medicine, Research Letter, medicine, Humans, Genetic Testing, Genetics (clinical), Multiple myeloma, Genetic testing, Incidental Findings, medicine.diagnostic_test, Maternal Serum Screening Tests, business.industry, Non invasive, Obstetrics and Gynecology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Sequence Analysis, DNA, medicine.disease, Research Letters, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Multiple Myeloma, business, Pregnancy Complications, Neoplastic
Abstract

What is already known about this subject? Non invasive prenatal testing for fetal trisomies 13, 18, and 21 occasionally identifies maternal cancer. What does this study add? A further case of maternal cancer incidentally diagnosed by routine NIPT. Extensive NIPT abnormalities are unlikely to be of fetal origin. Information given to patients should also adequately advise patients on potential incidental findings and might offer the option to opt out of receiving results beyond the trisomy report. International guidelines would improve patient counseling. ispartof: Prenatal Diagnosis vol:37 issue:12 pages:1257-1260 ispartof: location:England status: published

Published
2017

27. Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with<scp>l</scp>-asparaginase: The GRAALL experience

Author

Françoise Huguet, Patrice Chevallier, Pierre Bories, Oumedaly Reman, Mathilde Hunault-Berger, Norbert Ifrah, Xavier Thomas, Véronique Lhéritier, Aline Tanguy-Schmidt, Jamile Frayfer, Corentin Orvain, Victoria Cacheux, Etienne Daguindau, Caroline Bonmati, Felipe Suarez, Véronique Dorvaux, Laurence Sanhes, Marie-Anne Couturier, Hervé Dombret, Martine Escoffre-Barbe, and Jean-Michel Pignon

Subjects
medicine.medical_specialty, business.industry, Lymphoblastic lymphoma, Central nervous system, Antithrombin, Induction chemotherapy, Hematology, medicine.disease, Thrombosis, Gastroenterology, 3. Good health, Surgery, Venous thrombosis, medicine.anatomical_structure, Internal medicine, medicine, Adult Acute Lymphoblastic Leukemia, business, Complication, medicine.drug
Abstract

Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m2) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11–31) when patients had received a median of three l-ASP injections (range: 2–7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36–67%) at Day 17 (range: D3–D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4). Am. J. Hematol. 90:986–991, 2015. © 2015 Wiley Periodicals, Inc

Published
2015

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

Author

Sylvain Carras, Alexia Torroja, Anouk Emadali, Emilie Montaut, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Emmanuelle Tchernonog, Anna Schmitt, Roch Houot, Caroline Dartigeas, Sarah Barbieux, Selim Corm, Anne Banos, Ludovic Fouillet, Jehan Dupuis, Margaret Macro, Joel Fleury, Fabrice Jardin, Clementine Sarkozy, Ghandi Damaj, Pierre Feugier, Luc Matthieu Fornecker, Cecile Chabrot, Veronique Dorvaux, Krimo Bouabdallah, Sandy Amorim, Reda Garidi, Laurent Voillat, Bertrand Joly, Nadine Morineau, Marie Pierre Moles, Hacene Zerazhi, Jean Fontan, Yazid Arkam, Magda Alexis, Vincent Delwail, Jean Pierre Vilque, Loic Ysebaert, Barbara Burroni, Mary Callanan, Steven Le Gouill, and Rémy Gressin

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

Between 2011 and 2012, a phase II trial evaluated the use of the RiBVD (rituximab, bendamustine, velcade and dexamethasone) combination as first-line treatment for mantle cell lymphoma (MCL) patients over the age of 65. We have now re-examined the classic prognostic factors, adding an assessment of TP53 mutation status. Patients (N=74; median age 73 years) were treated with the RiBVD combination. Median progression-free survival (mPFS) was 79 months and median overall survival (mOS) was 111 months. TP53 mutation status was available for 54/74 (73%) patients. TP53 mutations (TP53mt) were found in 12 patients (22.2%). In multivariate analysis, among the prognostic factors (PF) evaluated, only TP53mt and an albumin level (Alb) 3.6 g/dL were independently associated with a shorter mPFS. A hazard ratio (HR) of 3.16 (1.3-9.9, P=0.014) was obtained for TP53mt versus TP53 wild-type (wt), and 3.6 (1.39-9.5, P=0.009) for Alb

Published
2023
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29. PS1377 IMPROVEMENT IN HEALTH-RELATED QUALITY OF LIFE FOR NEWLY DIAGNOSED MULTIPLE MYELOMA TRANSPLANT-ELIGIBLE PATIENTS TREATED WITH DARATUMUMAB, BORTEZOMIB, THALIDOMIDE, AND DEXAMETHASONE: CASSIOPEIA STUDY

Author

Murielle Roussel, Laurent Frenzel, Borhane Slama, Jean-Claude Eisenmann, Véronique Dorvaux, Carla Araujo, C. McKay, Saskia K. Klein, Sonja Zweegman, Michel Attal, Katharine S. Gries, C. Chaleteix, Mamoun Dib, Veronique Vanquickelberghe, Bruno Royer, Jessica Vermeulen, Pieter Sonneveld, Tobias Kampfenkel, Philippe Moreau, Annemiek Broijl, J. Trudeau, K.-S. Jie, Arnaud Jaccard, C. de Boer, and Kamel Laribi

Subjects
Oncology, Bortezomib/thalidomide, Health related quality of life, medicine.medical_specialty, business.industry, Daratumumab, Hematology, Newly diagnosed, medicine.disease, Internal medicine, medicine, business, Dexamethasone, Multiple myeloma, medicine.drug
Published
2019

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

Author

Mathieu Puyade, Karim Belhadj, Brigitte Kolb, Carla Araujo, Arnaud Jaccard, Michel Attal, Odile Luycx, Thomas Dejoie, Bruno Royer, Laurent Garderet, Sylvie Glaisner, Pascal Lenain, Denis Caillot, Anne-Marie Stoppa, Karim Laribi, Hélène Caillon, Jean-Claude Eisenmann, Hervé Avet-Loiseau, Lucie Planche, Pascal Godmer, Jean-Paul Fermand, Philippe Rodon, Murielle Roussel, Marc Wetterwald, Jean-Valère Malfuson, Gerald Marit, Martine Escoffre, Laetitia Biron, Philippe Moreau, Mamoun Dib, Jean Fontan, Thierry Facon, Driss Chaoui, Brigitte Pegourie, Carine Chaleteix, Borhane Slama, Cyrille Hulin, Mourad Tiab, Sabine Brechignac, Margaret Macro, Olivier Allangba, and Véronique Dorvaux

Subjects
Adult, Male, endocrine system, medicine.medical_specialty, Neutropenia, Immunology, Urology, Biochemistry, Dexamethasone, law.invention, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Randomized controlled trial, law, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Medicine, Humans, Prospective Studies, Prospective cohort study, Cyclophosphamide, Multiple myeloma, Aged, business.industry, Anemia, Cell Biology, Hematology, Middle Aged, medicine.disease, Thrombocytopenia, Surgery, Thalidomide, 030220 oncology & carcinogenesis, Female, business, Multiple Myeloma, 030215 immunology, medicine.drug
Abstract

The Intergroupe Francophone du Myelome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamide-dexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56.2% in the VCD arm (P = .05). In addition, the overall response rate was significantly higher in the VTD arm (92.3% vs 83.4% in the VCD arm; P = .01). Hematologic toxicity was higher in the VCD arm, with significantly increased rates of grade 3 and 4 anemia, thrombocytopenia, and neutropenia. On the other hand, the rate of peripheral neuropathy (PN) was significantly higher in the VTD arm. With the exception of hematologic adverse events and PN, other grade 3 or 4 toxicities were rare, with no significant differences between the VTD and VCD arms. Our data support the preferential use of VTD rather than VCD in preparation for ASCT. This trial was registered at www.clinicaltrials.gov as #NCT01564537 and at EudraCT as #2013-003174-27.

Published
2016

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

Author

Mourad Tiab, Xavier Leleu, Pascal Bourquard, Philippe Moreau, Laurent Voillat, Brigitte Kolb, Jean Fontan, Arnaud Jaccard, Marie-Odile Petillon, Thierry de Revel, Olivier Decaux, Philippe Rodon, Anna Schmitt, Jean Claude Eisenmann, Frédérique Kuhnowski, Véronique Dorvaux, Nathalie Meuleman, Gérard Lepeu, Damien roos Weil, Marie-Lorraine Chretien, Murielle Roussel, Olivier Fitoussi, Karim Belhadj-Merzoug, Michel Attal, Sophie Cereja, Thierry Facon, Catherine Humbrecht-Kraut, Lionel Karlin, Fritz Offner, Carla Araujo, Eric Voog, Jamile Frayfer, Pascal Lenain, Cyrille Hulin, Sophie Rigaudeau, Service d'Hématologie, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Hôpital Général de La Roche sur Yon, CRLCC Henri Becquerel, CHU Pontchaillou [Rennes], Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre hospitalier d'Avignon, CH Avignon, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Centre Hospitalier Chalon-sur-Saône William Morey, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier de Meaux, Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), Hôpital Universitaire de Vandoeuvre les Nancy, Laboratoire d'Hématologie [Rangueil], Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital de Rangueil, Service d'Hématologie Clinique, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Hôpital Claude Huriez, and Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille )

Subjects
Melphalan, Cancer Research, medicine.medical_specialty, [ SDV ] Life Sciences [q-bio], business.industry, Immunology, Cell Biology, Hematology, Newly diagnosed, medicine.disease, Biochemistry, Pulmonary hypertension, Carfilzomib, chemistry.chemical_compound, Peripheral neuropathy, Oncology, chemistry, Prednisone, Internal medicine, medicine, business, Intensive care medicine, Multiple myeloma, Febrile neutropenia, medicine.drug
Abstract

Background. New standards with increasing efficacy that are also characterized with improving the quality of life are needed for elderly myeloma patients. Although MPT and MPV regimens are remarkable in terms of efficacy, quality of life while on treatment with these 2 regimens remain an issue. The Carmysap twice weekly carfilzomib-based phase 2 study has demonstrated that Carfilzomib at the MTD of 36mg/m² might challenge bortezomib in the VMP standard. However, it has become routine practice to use bortezomib on a weekly schedule, with maintained efficacy and an improved safety profile. We sought to demonstrate that Carfilzomib Weekly plus Melphalan and Prednisone will prove strongly efficacious with acceptable safety profile and quality of life to newly diagnosed elderly multiple myeloma (eNDMM). Methods . IFM2012-03 (also called carmysap weekly) is a phase 1/2 multicenter open label single arm study to determine MTD during the phase 1 part and VGPR+CR rate during the phase 2 part of the study. The inclusion/exclusion criteria of interest were eNDMM (65 and older), with symptomatic and measurable disease, with absolute neutrophils ≥1 G/L, untransfused platelet count ≥75 G/L, hemoglobine ≥8.5 g/dL and clairance creatinine ≥ 30ml/min. We report herein the phase 1 part of the study which last cohort was completed at ASH abstract deadline. For the phase 1 part of the study, each cohort was 6 patients based, and started at 36mg/m² of carfilzomib on days 1, 8, 15, 22 using IV, 30 minutes infusion, route followed by a 13-day rest period per 35-days cycles, melphalan given at 0.25mg/kg/j and oral prednisone 60mg/m², both on days 1 to 4. The subsequent cohorts' doses for carfilzomib were 45, then 56 and finally 70mg/m². 9 cycles were planned as induction followed by a maintenance phase of weekly carfilzomib monotherapy given at 36mg/m² weekly for one year. The MTD was determined when ˃2 DLTs were observed. DLTs were considered during cycle 1 if any hematologic toxicity of grade 4 intensity or preventing administration of 2 or more of the 4 carfilzomib doses of the first treatment cycle, grade ≥3 febrile neutropenia, grade ≥3 gastrointestinal toxicities, any other grade ≥3 nonhematologic toxicity considered related to CMP by the principal investigator, grade ≥ 3 peripheral neuropathy persisting for more than 3 weeks after discontinuation of study drugs. Results. 26 NDMM patients recruited, 24 treated in the study, 6 per cohort at 36 mg/m² carfilzomib +MP, then 45 then 56, and finally at 70mg/m² which cohort cycle 1 is up and running. The median age was 74 with 10 patients older than 75 and sex ratio M/F 65. There was a DLT at 36 mg/m² carfilzomib (grade 4 lymphopenia), one at 45 (lysis syndrome complicated with grade 4 renal insufficiency, two at 56 (cardiac insufficiency grade 3 and febrile neutropenia grade 3). At ASH deadline, all patients from cohort 36 of carfilzomib have completed induction and maintenance up to cycle 6, 5/6 of cohort 45 have completed induction and started the maintenance phase, 5/6 of cohort 56 have completed cycle 6 of induction and pursue within the induction phase, and finally all patients from cohort 70 of carfilzomib are undergoing cycle 1. There are 22 SAE reported for a total of 171 cycles administered of carfilzomib +MP. So far, 3 patients (out of 24) have stopped treatment, including the 2 patients with DLTs, lysis syndrome and cardiac failure, and one patient that presented with pulmonary hypertension later in the disease course on cycle 5 of the 56mg/m² carfilzomib +MP cohort. And, an extra 3 patients have had Carfilzomib dose reduction, 2 patients at 36 from 45 and one at 45 from 56, for neutropenia grade 4, thrombocytopenia grade 4, and Dyspnea grade 3, respectively. Conclusion. The MTD of weekly carfilzomib in the combination to Melphalan and Prednisone could be determined at 70mg/m² in elderly NDMM, demonstrating the good safety profile of carfilzomib in this regimen and fragile population. The complete dataset of the entire study will be updated at ASH with response rate, survival and safety profile. Disclosures Leleu: Chugai: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; BMS: Honoraria; Novartis: Honoraria; TEVA: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Karlin:Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria. Fitoussi:Sandoz: Membership on an entity's Board of Directors or advisory committees. Moreau:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Published
2015

32. Light Chain Escape in Multiple Myeloma

Author

Jean Luc Harousseau, Benjamin Hebraud, Philippe Moreau, Brigitte Kolb, Anna Schmitt, Frédérique Kuhnowski, Michel Attal, Mourad Tiab, Sophie Cereja, Claire Mathiot, Pascal Bourquard, Thomas Dejoie, Philippe Rodon, Jean Fontan, Guillemette Fouquet, Brigitte Pegourie, Jean Claude Eisenmann, Catherine Humbrecht-Kraut, Denis Caillot, Hervé Avet-Loiseau, Laurent Garderet, Murielle Roussel, Damien Roos-Weil, Lionel Karlin, Olivier Decaux, Thierry Facon, Gérard Lepeu, Sophie Rigaudeau, Jean-Paul Fermand, Karim Belhadj, Arnaud Jaccard, Cyrille Hulin, Carla Araujo, Eric Voog, Jamile Frayfer, Pascal Lenain, Jean Valère Malfuson, Véronique Dorvaux, Nathalie Meuleman, Xavier Leleu, Laurent Voillat, and Marie Lorraine Chretien

Subjects
business.industry, Steering committee, Immunology, Cell Biology, Hematology, Missed diagnosis, Biochemistry, Management, Serum free, Median time, Large study, Standard test, Medicine, In real life, business
Abstract

Background. Progression by serum free light chain (sFLC) test without or preceding progression with intact immunoglobulin (Ig) is called light chain escape. This event alone is not considered a progression for patients with Multiple Myeloma (MM) according to International guidelines, although it is often considered a progression in real life and by clinical trials' investigators. We therefore sought to determine whether light chain escape would be a predictor of relapse and thus question a possible need to modify the current criteria for progression according to the International Myeloma Working Group (IMWG). Material and method. We have reviewed 325 (323 for analysis) patients that presented with a progression in the IFM/DFCI2009 phase 3 study (Attal et al. NEJM 2017). Among these 323 patients, 260 had initial tumor bulk measurement with intact Ig by serum protein electrophoresis test (SPEP; Ig ≥ 10 g/L) and 63 light chain MM (Ig < 10 g/L) measured using urine protein electrophoresis (UPEP). All progressions were validated in the central laboratory of CHU de Nantes (Dr T. Dejoie) and followed IMWG recommendations. sFLC increase was determined by absolute increase ≥ 100 mg/L and ≥ 25% from nadir value of the difference between involved and uninvolved FLC (ΔiFLC). Light chain escape was defined as sFLC increase without progression by SPEP (Ig increase ≥ 5 g/L and ≥ 25%) or UPEP (increase ≥ 200 mg/24h and ≥ 25%). Results. Among the 260 patients with intact Ig at diagnosis, 3 (1.15%) patients presented a light chain escape: progression by sFLC test without progression by SPEP. In parallel, 228 patients (87.7%) progressed by SPEP, of whom 18/228 (6.25%) showed a sFLC increase preceding the increase of intact Ig, with a median delay of 63 days. Among the 63 light chain MM, 6 (9.5%) patients presented a light chain escape: progression by sFLC test without progression by UPEP. Interestingly, 6 other patients (9.5%) progressed by SPEP even though Ig was < 10 g/L at diagnosis. Of the remaining 46 patients, 38 (60.3%) showed sFLC increase before progression by UPEP. Finally, 8 patients (12.7%) progressed but with intact Ig pauci-secreting MM meeting none of the M spike based progression criteria. Median time from iFLC nadir to ΔiFLC ≥ 100 mg/L was 280 days for light chain MM, 496 days for intact Ig MM, and 651 days for light chain escape. Median time from ΔiFLC ≥ 100 mg/L to follow-up visit to assess progression was 402 days light chain MM, 536 days for intact Ig MM, and 713 days for light chain escape. Overall, 9 (3%) patients had true light chain escape with progression by sFLC test without any other progression criteria. In parallel, in 56 (17%) patients, sFLC increase preceded progression to MM by standard test (SPEP or UPEP). Still the vast majority of patients had a regular relapse using the standard markers for progression. Conclusion. Based on a large study of patients treated into a phase 3 clinical trial with centralized assessment of response and progression, we showed that 20% of patients had progression by sFLC without meeting standard progression markers, of whom 3% had true light chain escape and 17% early light chain increase. Even though true light chain escape seems to be a rare phenomenon, analysis of sFLC test could help to avoid delayed or missed diagnosis of progression in 20% of patients in this clinical trial. This data should be confirmed in another database to assess whether a modification in the progression criteria in MM International guidelines should be proposed. Disclosures Hulin: Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Roussel:Amgen: Consultancy; Celgene: Consultancy; Takeda: Consultancy. Hebraud:Amgen: Consultancy; Janssen: Consultancy, Other: Lecture fees; travel and accommodation for congress, Research Funding; Sanofi: Consultancy; Takeda: Consultancy; Celgene: Consultancy, Other: Lecture fees, Research Funding. Karlin:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Belhadj:Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Decaux:Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Garderet:Amgen: Consultancy; Takeda: Consultancy; Celgene: Consultancy. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Avet-Loiseau:Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Moreau:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Attal:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janseen: Consultancy, Research Funding; Sanofi: Consultancy. Leleu:Karyopharm: Honoraria; Gilead: Honoraria; Incyte: Honoraria, Other: steering committee membership ; Roche: Honoraria; Sanofi: Honoraria, Other: steering committee membership steering committee membership ; Novartis: Honoraria, Other: steering committee membership ; Amgen: Honoraria, Other: steering committee membership ; Merk: Honoraria, Other: steering committee membership ; Takeda: Honoraria, Other: steering committee membership ; BMS: Honoraria, Other: steering committee membership ; Celgene: Honoraria, Other: steering committee membership ; Janssen: Honoraria, Other.

Published
2018

33. Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myélome (IFM)

Author

Philippe Moreau, Brigitte Kolb, Brigitte Pegourie, Bruno Royer, Jean-Yves Mary, Carla Araujo, Pascal Lenain, Denis Caillot, Gerald Marit, Hervé Avet-Loiseau, Christophe Fruchart, Edouard Randriamalala, Murielle Roussel, Anne-Marie Stoppa, Clotaire Danho, Claire Mathiot, Laurent Garderet, Cyrille Hulin, Mammoun M. Dib, Michel Attal, Anne Huynh, Jean-Luc Harousseau, and Véronique Dorvaux

Subjects
Adult, Male, Oncology, Melphalan, medicine.medical_specialty, Transplantation Conditioning, Immunology, Phases of clinical research, Antineoplastic Agents, Transplantation, Autologous, Biochemistry, Bortezomib, Autologous stem-cell transplantation, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Multiple myeloma, Aged, Demography, Dose-Response Relationship, Drug, business.industry, Cell Biology, Hematology, Middle Aged, medicine.disease, Boronic Acids, Survival Analysis, Surgery, Transplantation, Case-Control Studies, Pyrazines, Disease Progression, Proteasome inhibitor, Female, France, Multiple Myeloma, business, Stem Cell Transplantation, medicine.drug
Abstract

Autologous stem cell transplantation (ASCT) is recommended for younger patients with newly diagnosed multiple myeloma. Achieving complete response (CR) or at least very good partial response (VGPR) is a major prognostic factor for survival with 20% to 30% of patients achieving CR after ASCT. Bortezomib has shown synergistic effects with melphalan and no prolonged hematologic toxicity. In this Intergroupe Francophone du Myelome (IFM) phase 2 study, 54 untreated patients were enrolled between July and December 2007 to receive bortezomib (1 mg/m2 × 4) and melphalan (200 mg/m2) as conditioning regimen (Bor-HDM). Overall, 70% of patients achieved at least VGPR, including 17 patients with CR (32%) after ASCT. No toxic deaths were observed. Bortezomib did not increase hematologic toxicity. Only 1 grade 3 to 4 peripheral neuropathy was reported. A matched control analysis was conducted comparing our cohort with patients from the IFM 2005-01 trial (HDM alone). Patients were matched for response to induction therapy and type of induction: CR was higher in the Bor-HDM group (35% vs 11%; P = .001), regardless of induction therapy. These results suggest that Bor-HDM is a safe and promising conditioning regimen. Randomized studies are needed to assess whether this conditioning regimen is superior to HDM alone. This trial was registered at [www.clinicaltrials.gov][1] as [NCT00642395][2]. [1]: http://www.clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00642395&atom=%2Fbloodjournal%2F115%2F1%2F32.atom

Published
2010

34. Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials

Author

Frédéric Garban, Hervé Avet-Loiseau, Serge Leyvraz, Denis Caillot, C Chaleteix, Brigitte Kolb, T. Lamy, Bernard Grosbois, Mauricette Michallet, Catherine Traullé, Marc Wetterwald, Claire Mathiot, Ibrahim Yakoub-Agha, Chantal Doyen, M. Mohty, J L Harousseau, Mamoun Dib, Véronique Dorvaux, Lotfi Benboubker, M. Attal, Jean-Gabriel Fuzibet, Thierry Facon, Gerald Marit, Philippe Moreau, Christian Berthou, Laurent Garderet, C. Hulin, Jérôme Jaubert, and Philippe Casassus

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Long term follow up, Gastroenterology, Dexamethasone, Disease-Free Survival, Translocation, Genetic, Genetic Heterogeneity, Hemoglobins, Intensive therapy, Immunopathology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Multiple myeloma, Aged, Retrospective Studies, Chromosomes, Human, Pair 14, Very Good Partial Response, Hematology, business.industry, Cytarabine, Middle Aged, Prognosis, medicine.disease, Surgery, Transplantation, Clinical trial, Oncology, Vincristine, Multivariate Analysis, Female, Chromosomes, Human, Pair 4, Multiple Myeloma, beta 2-Microglobulin, business, Follow-Up Studies
Abstract

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin4 mg/l and high hemoglobin (Hb)/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

Published
2007

35. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy

Author

Bernard Grosbois, Marc Renaud, H. Orfeuvre, Antoine Thyss, Michel Blanc, Jean-Luc Harousseau, Jean-Yves Mary, Gérard Lepeu, Cyrille Hulin, Marc Wetterwald, Véronique Dorvaux, Ibrahim Yakoub-Agha, Thierry Facon, Philippe Casassus, Jean-Paul Eschard, A Sadoun, Jean-François Rossi, Mathieu Monconduit, M C Vekemans, Brigitte Pegourie, Laurent Voillat, Jérôme Jaubert, Hervé Maisonneuve, Beatrice Thielemans, Frédéric Maloisel, Isabelle Azais, Michel Attal, Chantal Doyen, Augustin Ferrant, Jacques Troncy, Régis Bataille, Philippe Collet, Houchingue Eghbali, and Bruno Anglaret

Subjects
Male, Melphalan, medicine.medical_specialty, medicine.drug_class, Immunology, Context (language use), Infections, Biochemistry, Dexamethasone, Disease-Free Survival, law.invention, Randomized controlled trial, Prednisone, law, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Survival analysis, Multiple myeloma, Aged, Neoplasm Staging, business.industry, Patient Selection, Interferon-alpha, Cell Biology, Hematology, medicine.disease, Survival Analysis, Surgery, Treatment Outcome, Corticosteroid, Female, Multiple Myeloma, business, medicine.drug
Abstract

Dexamethasone alone increases life expectancy in patients with relapsed multiple myeloma (MM); however, no large randomized study has compared dexamethasone and dexamethasone-based regimens with standard melphalan-prednisone in newly diagnosed MM patients ineligible for high-dose therapy. In the Intergroupe Francophone du Myelome (IFM) 95-01 trial, 488 patients aged 65 to 75 years were randomized between 4 regimens of treatment: melphalan-prednisone, dexamethasone alone, melphalan-dexamethasone, and dexamethasone-interferon alpha. Response rates at 6 months (except for complete response) were significantly higher among patients receiving melphalan-dexamethasone, and progression-free survival was significantly better among patients receiving melphalan (P < .001, for both comparisons), but there was no difference in overall survival between the 4 treatment groups. Moreover, the morbidity associated with dexamethasone-based regimens was significantly higher than with melphalan-prednisone, especially for severe pyogenic infections in the melphalan-dexamethasone arm and hemorrhage, severe diabetes, and gastrointestinal and psychiatric complications in the dexamethasone arms. Overall, these results indicated that dexamethasone should not be routinely recommended as first-line treatment in elderly patients with MM. In the context of the IFM 95-01 trial, the standard melphalan-prednisone remained the best treatment choice when efficacy and patient comfort were both considered. These results might be useful in the context of future combinations with innovative drugs.

Published
2006

36. Le hasard fait parfois mal les choses !

Author

M. Cabon, Véronique Dorvaux, A. Valois, Bruno Graffin, Philippe Carassou, J.-M. Puyhardy, Gaël Cinquetti, X. Roux, C. Cuvelier, Serge Védy, and J. Schmidt

Subjects
Gastroenterology, Internal Medicine
Abstract

Service de medecine interne, hopital d’instruction des armees Legouest, 27, avenue de Plantieres, BP 90001, 57077 Metz cedex 3, France Service de biologie medicale, hopital d’instruction des armees Legouest, 27, avenue de Plantieres, BP 90001, 57077 Metz cedex 3, France Service d’hematologie clinique, hopital Bon Secours, 1, place Ph.-de-Vigneulles, 57038 Metz cedex 01, France Service de medecine interne, hopital Nord, CHU d’Amiens, 2, place Victor-Pauchet, 80054 Amiens, France

Published
2013

37. Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial

Author

Margaret Macro, Thierry Facon, Christian Berthou, Norbert Najman, Gerald Marit, Denis Caillot, Bernard Rio, Thomas Matthes, Lotfi Benboubker, Michel Attal, Philippe Casassus, Jean-Jacques Sotto, Chantal Doyen, François Guilhot, Bernard Grosbois, Laurent Voillat, Philippe Moreau, Jérôme Jaubert, Jean-Luc Harousseau, Frédéric Maloisel, Véronique Dorvaux, Cyrille Hulin, Bernard Pignon, Jean-Gabriel Fuzibet, M. Monconduit, Sylvie François, Mauricette Michallet, and Régis Bataille

Subjects
Adult, Male, Melphalan, medicine.medical_specialty, Transplantation Conditioning, medicine.medical_treatment, Immunology, VAD Regimen, Transplantation, Autologous, Biochemistry, Autologous stem-cell transplantation, medicine, Mucositis, Humans, Prospective Studies, Antineoplastic Agents, Alkylating, Multiple myeloma, Aged, Chemotherapy, business.industry, Graft Survival, Remission Induction, Hematopoietic Stem Cell Transplantation, Cell Biology, Hematology, Middle Aged, Total body irradiation, medicine.disease, Combined Modality Therapy, Survival Analysis, Surgery, Regimen, Treatment Outcome, Female, Multiple Myeloma, business, Whole-Body Irradiation, medicine.drug
Abstract

High-dose therapy has become a common treatment for myeloma. The objective of this study (Intergroupe Francophone du Myélome [IFM] 9502 trial) was to compare in a prospective and randomized trial the 2 most widely used conditioning regimens before autologous stem cell transplantation in newly diagnosed symptomatic patients younger than 65 years old: 8 Gy total body irradiation plus 140 mg/m(2) melphalan (arm A) versus 200 mg/m(2) melphalan (arm B). A total of 282 evaluable patients were compared--140 in arm A and 142 in arm B. Baseline characteristics and disease response to 4 cycles of the VAD regimen performed before randomization and autologous stem cell transplantation were identical in the 2 treatment arms. In arm B, hematologic recovery was significantly faster for both the duration of neutropenia and thrombocytopenia, transfusion requirements were also significantly lower, and the median duration of hospitalization was significantly shorter. In arm A, the incidence of severe mucositis was significantly increased. The median duration of event-free survival was similar in both arms (21 vs 20.5 months, P =.6), but the 45-month survival was 65.8% in arm B versus 45.5% in arm A (P =.05). This difference might be attributed in part to better salvage regimens after relapse in arm B compared with arm A. We conclude that 200 mg/m(2) melphalan is a less toxic and at least as effective conditioning regimen when compared with 8 Gy total body irradiation with 140 mg/m(2) melphalan. This regimen should be considered as the standard of care before autologous stem cell transplantation in multiple myeloma.

Published
2002

38. Acute myelomonocytic leukemia revealed by a chickenpox-like rash

Author

Philippe Canton, Bruno Hoen, Francis Witz, Catherine Aghassian, Véronique Dorvaux, and Anne C Neidhardt

Subjects
Pathology, medicine.medical_specialty, Chickenpox, Unusual case, integumentary system, medicine.diagnostic_test, business.industry, virus diseases, Leukemia cutis, Dermatology, medicine.disease, Rash, Infectious Diseases, medicine.anatomical_structure, Skin biopsy, Acute myelomonocytic leukemia, medicine, Bone marrow, medicine.symptom, business, Infiltration (medical)
Abstract

An unusual case of leukemia cutis is presented. A 42-year-old man presented with a vesicular skin rash mimicking chickenpox. Skin biopsy firmly ruled out the diagnosis of varicella and revealed an infiltration of the superficial derma by myeloblasts. Bone marrow aspirates confirmed the diagnosis of acute myelomonocytic leukemia (type M4).

Published
1996

39. Agranulocytoses aiguës médicamenteuses. Étude clinique à propos de 30 patients et évolution des étiologies sur 2 décennies

Author

Véronique Dorvaux, A Guerci, V Stockemer, P. Lederlin, J.F. Paitel, and F. Witz

Subjects
Gynecology, medicine.medical_specialty, business.industry, Gastroenterology, Internal Medicine, medicine, business
Abstract

Resume Entre 1982 et 1993, 30 patients ont ete hospitalises pour une agranulocytose aigue presumee d'origine medicamenteuse. Aucun patient n'avait recu de chimiotherapie antitumorale ou de radiotherapie dans les 6 mois precedant l'episode. On note une predominance feminine (21 femmes, neuf hommes). L'âge moyen est de 59,3 ans. Le medicament en cause a pu etre retrouve dans 25 cas dont noramidopyrine cinq cas, antithyroidiens de synthese quatre cas, antiinflammatoires non steroidiens quatre cas. Cinq patients (17%) sont decedes d'infection au cours de l'agranulocytose. Dans trois cas, l'infection a pu etre documentee. Un facteur de croissance hematopoietique a ete utilise chez deux patients. Le nombre de polynucleaires neutrophiles atteignait 0,5.10 9 /1 en 2 a 14 jours apres le diagnostic et 1.10 9 /1 en 3 a 16 jours. La neutropenie a moins de 0,5.10 9 /1 est significativement plus courte ( p = 0,008) dans les cas ou le myelogramme montrait une moelle riche avec blocage de maturation plutot qu'une hypoplasie granuleuse. Comparee a une etude analogue faite dans le meme service entre 1971 et 1981, on assiste a une diminution du nombre de cas par annee; les etiologies de ces agranulocytoses se sont modifiees: les phenicoles ne sont plus en cause, les cas imputables a la noramidopyrine regressent. Actuellement les antithyroidiens de synthese deviennent une des principales etiologies.

Published
1995

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

Author

Kamel Laribi, Driss Chaoui, Mourad Tiab, Sabine Brechignac, Philippe Moreau, Lucie Planche, Pascal Godmer, Laetitia Biron, Margaret Macro, Cyrille Hulin, Hervé Avet-Loiseau, Karim Belhadj, Murielle Roussel, Marc Wetterwald, Hélène Caillon, Arnaud Jaccard, Gerald Marit, Thomas Dejoie, Brigitte Pegourie, Odile Luycx, Thierry Facon, Denis Caillot, Pascal Lenain, Mamoun Dib, Jean Fontan, Carine Chaleteix, Borhane Slama, Anne-Marie Stoppa, Olivier Allangha, Mathieu Puyade, Véronique Dorvaux, Jean-Paul Fermand, Michel Attal, Martine Escoffre, Carla Araujo, Brigitte Kolb, Bruno Royer, Jean Claude Eisenmann, Laurent Garderet, Sylvie Glaisner, and Philippe Rodon

Subjects
medicine.medical_specialty, business.industry, Immunology, Cell Biology, Hematology, medicine.disease, Biochemistry, law.invention, Thalidomide, Clinical trial, Regimen, Autologous stem-cell transplantation, Randomized controlled trial, law, Internal medicine, medicine, Clinical endpoint, Progression-free survival, business, Multiple myeloma, medicine.drug
Abstract

Background Induction therapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with symptomatic multiple myeloma less than 66 years old. The quality of response to the induction treatment is an important prognostic factor and is predictive of progression free survival (PFS) following ASCT. The triplet combinations bortezomib-thalidomide-dexamethasone (VTD) and bortezomib-cyclophosphamide-dexamethasone (VCD) have demonstrated high response rates in prospective phase 2 and phase 3 clinical trials, they are 2 of the most commonly used induction regimens prior to ASCT, and are both recommended in the International guidelines. To date, no comparative data from prospective randomized trials of the safety and efficacy of VTD vs VCD are available. This provided the rationale for the phase 3 investigation of VTD vs VCD prior to ASCT in patients with de novo MM in this randomized multicenter study (NCT01564537). Methods Patients with de novo symptomatic MM less than 66 years old were prospectively randomized to receive either 4 cycles of VTD (arm A) or 4 cycles of VCD (arm B) followed by ASCT. The VTD regimen consisted of four 21-day cycles of bortezomib 1.3 mg/m²/d, subcutaneously (SC) D1, 4, 8 and 11, Dexamethasone 40 mg/d, PO D1 to 4, D9 to 12 and Thalidomide 100 mg/d, PO D1 to D21. The VCD regimen consisted of four 21-day cycles of bortezomib 1.3 mg/m²/d, SC D1, 4, 8 and 11, Dexamethasone 40 mg/d, PO D1 to 4, D9 to 12 and Cyclophosphamide 500 mg/m²/d, PO D1, 8, 15. Patients were stratified according to ISS (1-2 versus 3) and cytogenetics (high-risk defined by 17p deletion and t(4;14) versus other).The primary endpoint was very good partial response (VGPR) rate following 4 cycles. Response was assessed in a central lab according to the IMWG criteria. Assuming a VGPR rate of 60% in the VTD arm versus 45% in the VCD arm (15% difference), the possibility to detect a statistically significant difference required the enrolment of 340 patients overall (170 per arm). Adverse events were graded using the NCI CTCAE catalogue, version 4.0. Results From 11/2013 to 02/2015, 358 patients were enrolled into the study. 18 were screening failures, and 170 were randomized each to arm A (VTD) and arm B (VCD). The median age was 60 years (range, 26-65), 62% of the patients were male, and overall, the patient characteristics were well-balanced across the 2 arms of the study. The median number of induction cycles administered in both arms was 4 (1-4). On an intent-to-treat basis, the overall response rate (> partial response [PR]) was 92.3% in arm A, including a 10.7% complete response (CR) rate and a VGPR rate of 66.7%, while in arm B the overall response rate was 84%, with a 9.5% CR and a 56.2% VGPR rate. VGPR and PR rates were significantly higher in the VTD arm with p-values of 0.04 and 0.02, respectively. Seven patients died during induction therapy (2%), 3 in arm A from infections (2) and pulmonary embolism (1), and 4 in arm B from progression to extramedullary myeloma (2) and infections (2). Grades 3 / 4 peripheral neuropathy occurred in 4% and 2.2% in Arm A and B, respectively. Grade 3/4 neutropenia was seen in 11.9% vs 22.5% in Arm A and B, respectively. Conclusion This trial is the first prospective randomized comparison of 4 cycles of VTD versus 4 cycles of VCD administered as induction therapy prior to ASCT. VTD was shown to be significantly superior to VCD in terms of VGPR and PR rates. Neuropathy rates low in both arms, while neutropenia was more frequent with VCD. Disclosures Moreau: Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hulin:Celgene Corporation: Honoraria; Janssen: Honoraria; Bristol Myers Squibb: Honoraria; Amgen: Honoraria. MACRO:celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees. Garderet:Bristol-Myers Squibb: Consultancy. Stoppa:Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees. Laribi:Hospira SAS: Research Funding. Avet-Loiseau:jansen: Membership on an entity's Board of Directors or advisory committees; onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees; onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Attal:jansen: Honoraria; celgene: Membership on an entity's Board of Directors or advisory committees.

Published
2015

41. How to Treat Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Patients : Results on 86 Patients of the French BPDCN Network

Author

Philippe Saas, Elise Robert, Yohan Desbrosses, Anne-Claire Gac, Tony Marchand, Jean-Valère Malfuson, Mathieu Puyade, Jean-Pierre Marolleau, Denis Caillot, Delphine Binda, Michel Maigre, Anne-Sophie Michallet, Denis Guyotat, Lila Gilis, Eric Deconinck, Remy Gressin, Damien Roos-Weil, Carole Soussain, Christian Recher, Felipe Suarez, Aurore Pugin, Bernard Bonnotte, Fabrice Jardin, Etienne Lengliné, Francine Garnache Ottou, Pierre Peterlin, Sophie Dalac, Berengere Gruson, Bernard Drenou, Maïder Pagadoy, Didier Bouscary, Pascal Turlure, Thorsten Braun, Eric Pujade-Lauraine, Fanny Angelot Delettre, Eve Poret, Pierre-Simon Rohrlich, Chrystelle Vidal, Sabeha Biichle, Yazid Arkam, Véronique Dorvaux, Laure Philippe, Caroline Bonmati, Franck Leroux, Louis Benazet, Anne Roggy, and Bruno Lioure

Subjects
medicine.medical_specialty, Myeloid, business.industry, medicine.medical_treatment, Immunology, Myeloid leukemia, Cell Biology, Hematology, Hematopoietic stem cell transplantation, medicine.disease, Biochemistry, Gastroenterology, Surgery, Transplantation, Log-rank test, medicine.anatomical_structure, Internal medicine, Acute lymphocytic leukemia, medicine, Methotrexate, business, Dexamethasone, medicine.drug
Abstract

Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive neoplasm for which there is still no current consensus on the best therapeutic approach. Most patients respond to intensive chemotherapy, but relapses are almost inevitable with median overall survival (OS) in the largest patient series ranging from 8 to 12 months except for patients who could benefit from allogenic hematopoietic stem cell transplantation (allo-HSCT). We present results of the first line treatments used in France between 2000 and 2013 for 86 patients recruited in the French network of BPDCN (abstract ASH 2015 N°78460). Seventeen patients were treated with acute lymphoid leukemia (ALL)-like therapy (median age : 63 yo) , 19 with acute myeloid leukemia (AML)-like therapy (median age : 40 yo), 16 patients with CHOP-like therapy (median age : 72 yo), 16 patients with NK/T-like therapy (based on high-dose methotrexate and L-asparaginase, ± dexamethasone, median age: 59 yo), and 12 patients received "other treatments" (OT, means variable drugs, median age : 82 yo). Thirty four patients obtained a complete remission (CR) and received HSCT (autologous n=4, or allogeneic n=30). The response rates for CHOP-like and OT groups were 31.3% and 25.0% respectively. For ALL-like, AML-like, and NK/T-like groups, response rates reached 70.6%, 78.9%, and 62.5% respectively (no statistic difference). Relapse rates among responders for CHOP-like and OT groups were 60% and 33.3% whereas there were only 25%, 26.7%, and 20% in ALL-like, AML-like, and NK/T-like groups respectively. For patients who obtained remission, the median of remission duration was 8.0 and 14.0 months for patients who received CHOP-like treatments (n=5) and OT (n=3) respectively and 10.0, 10.0, and 9.0 months for ALL-like (n=11), AML-like (n=14), and NK/T-like groups (n=9) respectively (p = 0.6339). In preclinical studies, we have shown that BPDCN cells are sensitive in vitro to idarubicine (Angelot Delettre F et al, 2015) so we studied patients receiving idarubicine in first line therapy in our series (n=9). From these 9 patients, 7 obtained CR and only one relapsed after 10 months. The 6 patients in continuous CR without any relapse have received HSCT (allo, n=5 or auto, n=1). Two out of those 6 patients are alive at the time of data collection with a follow-up of 40 and 87 months; the other 4 patients died after the graft, one relapsed after auto-HSCT, and 3 died of infectious complications after allo-HSCT. The median OS for patients who received HSCT, auto or allo (n=34) and other patients (n = 52) is respectively 49 and 8 months (p < 0.0001, Figure 1). The beneficial effect of HSCT persists independently of age in multivariate analysis. These results suggest that NK/T-like, AML-like, and ALL-like groups give better results than CHOP-like and OT groups. However, there is no significant statistical difference between AML-like, ALL-like, and NK/T-like groups. Thus it seems to be wise to combine "lymphoid" drugs like methotrexate, L-asparaginase and dexamethasone with "myeloid" drug such as idarubicine. The importance of allogenic stem cell transplantation to sustain remission is clear in this study and other one (Roos-Weil et al, 2013). We also observed a prolonged CR in one patient after auto-HSCT. Based on our results, we will propose the first prospective, multicentric, phase II trial in BPDCN, testing a combination of 3 cycles of methotrexate, L-asparaginase, idarubicine and dexamethasone followed by an allo-HSCT in first clinical remission for all eligible patients or repeated cycle of these drugs for unfit patients with auto-HSCT if possible. Kaplan-Meier overall survival curves compared by the Log-Rank test in the cohort of 34 HSCT patients (auto and allo, blue line) and 52 non HSCT patients (red line) (p Figure 1. Overall survival of HSCT patients and non HSCT patients. Figure 1. Overall survival of HSCT patients and non HSCT patients. Disclosures Recher: Celgene; Amgen; Chugai: Research Funding; Janssen; Novartis; Amgen: Other: Travel, accommodations, expenses; Sunesis; Celgene: Consultancy. Deconinck:CHUGAI: Other: Travel for international congress; NOVARTIS: Other: Travel for international congress; ALEXION: Other: Travel for international congress; LFB loboratory: Consultancy; JANSSEN: Other: Travel for international congress; PFIZER: Research Funding; ROCHE: Research Funding.

Published
2015

42. [Biclonal or biphenotypic chronic lymphotic leukemia? An answer brought by the treatment]

Author

Véronique Dorvaux, Anne Staal, J. Didion, Y. Rio, Céline Acker, Véronique Latger-Cannard, and Cédric Aumont

Subjects
Male, Chronic lymphocytic leukemia, Clone (cell biology), General Medicine, CD79B, Biology, Middle Aged, medicine.disease, Immunoglobulin light chain, Molecular biology, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Immunophenotyping, Phenotype, immune system diseases, Drug Resistance, Neoplasm, hemic and lymphatic diseases, Monoclonal, medicine, Humans, CD5
Abstract

A 51-years-old patient with polyadenopathies presents a non monotypic chronic lymphocytic leukemia (CLL): lymphocytes B CD5+, CD23+, CD22-,CD79b dim, FMC7- express κ (71%) and λ (21%) light chains without coexpression. The caryotype shows two clones with one in evolution. Lymphoid clonality analysis by PCR (polymerase chain reaction) of the heavy and light chains genes of immunoglobulins shows two monoclonal rearrangements for each kind of chains. Lack of lymphoid cells sorting in function of the light chain doesn't allow us to conclude between a biclonal CLL and a biallelic monoclonal CLL. New adenopathies appearance in this patient, one year and a half after the end of his chemotherapy, leads to realisation of a new immunophenotyping: CLL is now monotypic with κ light chains expressed at 95%. In the new caryotype, only one clone is still present: it is the clone in evolution in the first caryotype and which presents additional abnormalities. This evolution allows us to assert the biclonality of the primitive CLL, the two clones evolving differently under treatment. In conclusion, the patient presented a biclonal CLL with one clone responding to treatment and the other one resistant.

Published
2011

43. Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexaméthasone

Author

Ibrahim Yakoub-Agha, P. Moreau, Jean Soulier, J. P. Fermand, Véronique Dorvaux, Hervé Avet-Loiseau, Mag groups, M. Attal, C. Hulin, Karim Belhadj, Stephane Minvielle, and Laurent Garderet

Subjects
Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Dexamethasone, Bortezomib, Refractory, Internal medicine, medicine, Humans, Lenalidomide, Aged, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, Chromosome Aberrations, Chemotherapy, Hematology, business.industry, Middle Aged, Boronic Acids, Surgery, Thalidomide, Treatment Outcome, Pyrazines, Multivariate Analysis, Corticosteroid, Drug Therapy, Combination, Female, business, Multiple Myeloma, medicine.drug
Abstract

This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels

Published
2010

44. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial

Author

Jacques Troncy, Michel Attal, Chantal Doyen, Jean Yves Mary, Brigitte Kolb, Lotfi Benboubker, Mamoun Dib, Claire Mathiot, Cyrille Hulin, Philippe Casassus, H. Jardel, Hervé Avet-Loiseau, Ibrahim Yakoub-Agha, Claude Martin, Mathieu Monconduit, Thierry Facon, Gaelle Guillerm, Carine Chaleteix, Bernard Grosbois, Brigitte Pegourie, Marc Renaud, Véronique Dorvaux, Laurent Voillat, Bruno Anglaret, Jean Luc Harousseau, Jérôme Jaubert, and Hervé Maisonneuve

Subjects
Melphalan, Male, medicine.medical_specialty, Urology, Autologous stem-cell transplantation, MPT Regimen, Prednisone, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Antineoplastic Agents, Alkylating, Multiple myeloma, Aged, business.industry, Combination chemotherapy, General Medicine, medicine.disease, Surgery, Thalidomide, Transplantation, Survival Rate, Female, business, Multiple Myeloma, Immunosuppressive Agents, medicine.drug, Stem Cell Transplantation
Abstract

Background In multiple myeloma, combination chemotherapy with melphalan plus prednisone is still regarded as the standard of care in elderly patients. We assessed whether the addition of thalidomide to this combination, or reduced-intensity stem cell transplantation, would improve survival. Methods Between May 22, 2000, and Aug 8, 2005, 447 previously untreated patients with multiple myeloma, who were aged between 65 and 75 years, were randomly assigned to receive either melphalan and prednisone (MP; n=196), melphalan and prednisone plus thalidomide (MPT, n=125), or reduced-intensity stem cell transplantation using melphalan 100 mg/m(2) (MEL100; n=126). The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00367185. Findings After a median follow-up of 51.5 months (IQR 34.4-63.2), median overall survival times were 33.2 months (13.8-54.8) for MP, 51.6 months (26.6-not reached) for MPT, and 38.3 months (13.0-61.6) for MEL100. The MPT regimen was associated with a significantly better overall survival than was the MP regimen (hazard ratio 0.59, 95% CI 0.46-0.81, p=0.0006) or MEL100 regimen (0.69, 0.49-0.96, p=0.027). No difference was seen for MEL100 versus MP (0.86, 0.65-1.15, p=0.32). Interpretation The results of our trial provide strong evidence to indicate that the use of thalidomide in combination with melphalan and prednisone should, at present, be the reference treatment for previously untreated elderly patients with multiple myeloma.

Published
2007

45. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome

Author

Catherine Thieblemont, Jean-Luc Harousseau, Anne-Marie Stoppa, Marc Renaud, Frédéric Garban, Marc Wetterwald, Véronique Dorvaux, Ibrahim Yakoub-Agha, Denis Caillot, Philippe Moreau, Mauricette Michallet, Cyrille Hulin, Bernard Grosbois, Thierry Facon, Claire Mathiot, Laurent Voillat, Marc Zandecki, Gerald Marit, Philippe Casassus, Jean-Jacques Sotto, Catherine Charbonnel, Régis Bataille, Jean-Gabriel Fuzibet, Serge Leyvraz, Gaelle Guillerm, Hervé Avet-Loiseau, Mathieu Monconduit, Lotfi Benboubker, Lucienne Michaux, Laurent Garderet, Michel Attal, Stephane Minvielle, Charles Dumontet, and Isabelle Azais

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Pathology, Adolescent, Immunology, Biochemistry, Models, Biological, Disease-Free Survival, Immunopathology, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Child, Survival rate, Multiple myeloma, Neoplasm Staging, Chromosome Aberrations, Hematology, medicine.diagnostic_test, business.industry, Infant, Newborn, Infant, Cell Biology, Middle Aged, medicine.disease, Survival Rate, medicine.anatomical_structure, Child, Preschool, Female, Bone marrow, Hyperdiploidy, France, business, Multiple Myeloma, Fluorescence in situ hybridization, Follow-Up Studies
Abstract

Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with β2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.

Published
2007

46. Frontline Therapy with the Ribvd Regimen Elicits High Clinical and Molecular Response Rates and Long PFS in Elderly Patients Mantle Cell Lymphoma (MCL); Final Results of a Prospective Phase II Trial By the Lysa Group

Author

Hacene Zerazhi, Loic Ysebaert, Remy Gressin, Ghandi Damaj, Bertrand Joly, Jean Pierre Vilque, Guillaume Cartron, Cecile Chabrot, Krimo Bouabdallah, Yazid Arkam, Fabrice Jardin, Marie Pierre Moles, Jean Michel Pignon, Véronique Dorvaux, Christiane Mounier, Jehan Dupuis, Selim Corm, Roch Houot, J. Fleury, Margareth Macro, Katell Le Du, Lionel Karlin, Nicolas Daguindau, Nadine Morineau, Laurent Voillat, Magda Alexis, Reda Garidi, Sylvain Carras, Mary Callanan, Jean Fontan, Anne Banos, Luc Fornecker, Pierre Feugier, Sandy Amorin, Steven Le Gouill, Caroline Dartigeas, Adrian Tempescul, and Vincent Delwail

Subjects
Bendamustine, medicine.medical_specialty, business.industry, Immunology, Phases of clinical research, Cell Biology, Hematology, Neutropenia, medicine.disease, Biochemistry, Gastroenterology, Surgery, Regimen, Maintenance therapy, Internal medicine, medicine, Rituximab, Mantle cell lymphoma, business, Febrile neutropenia, medicine.drug
Abstract

Background: Eight RCHOP/21 cycles followed by Rituximab maintenance is considered the standard of care for first line therapy in elderly MCL patients in Europe (1). However,complete clinical (CR) and molecular responses (MR) to therapy remain suboptimal(CR rate 30-35%, MR after 8 cycles 67 %). Regimen combining Rituximab and Bendamustine and more recently proteasome inhibitor Bortezomib (Velcade®) with CHOP regimen (VcR-CAP) demonstrated superior CR rates and PFS compared to R-CHOP. We have investigated the RiBVD regimen (Rituximab, Bendamustine,Velcade® and Dexamethasone) in a prospective phase II trial by the LYSA group. Aims of the study: The primary objective was to improve the median PFS by 6 months over the current 18 months PFS obtained with RCHOP when given without maintenance (ref Lenz, JCO 2005). The secondary objectives were to investigate the prognostic impact of molecular and FDG-PET responses on survival.. Methods and Material: All patients aged 65 or older with a diagnosis of MCL were treated by the RiBVD regimen if they fulfilled the following inclusion criteria: AAstage II-IV, PS < 3, no other neoplasm, no active HIV or HBV or HCV infections, no renal (creatinin clearance > 20ml/mn) or cardiac dysfunction, no diabetes. The RiBVD regimen was administered every 4 weeks with Rituximab 375 mg/m² IV on day(D)1, Bendamustine 90 mg/m² IV on D1, 2, Dexamethasone 40 mg IV on D2 and Bortezomib (Velcade®) 1.3 mg/m² subcutaneously on D1, 4, 8 and 11. Primary prophylaxis with valacyclovir was mandatory for Herpes virus reactivation, but there was no recommendation for bacterial prevention. Patients were scheduled to receive a total of 6 cycles, if they achieved at least PR at 4 cycles. The IWG criteria, with and without FDG-PET, were used to define responses after 4 and 6 cycles. FDG-PET response was evaluated in each center with the five-point scale visual method of Deauville. Molecular responses (MR) were evaluated centrally by RQ-PCR using patient specific IGH VDJ targets as previously described (2). Results: Seventy six patients were recruited in one year (from November 2011 to December 2012), 74 were evaluable [2 patients were excluded because HBV positivity (n=1) or misdiagnosis (n=1)]. Fifty four samples were centrally reviewed for diagnosis, 45 were classic form of MCL, 9 pleomorphic variant and one patient had a DLBCL. Clinical characteristics of the 74 patients were: Median age 73 yo (64-83), sex ratio M/F = 2 (49/25), AAstage II/III-IV = 4/70, PS 0-1/2 = 63/11, MIPIscore low/intermediate/high= 3/19/50 (2 undetermined). The median follow-up is 21 months. Thirteen patients died because of lymphoma progression (n=7), cardiac arrest (n=2) or in one case each,pneumonia, Progressive Multifocal LeukoEncephalopathy, pancreatic carcinoma or of unknown causes. After 4 cycles the ORR was 86% (n=64) and CR/CRu 57% (n=42). After 6 cycles, the CR/CRu raised to 74% (n=55) the PR rate was 9% (n=7), 2 patients had a stable disease, 4 progressed and 5 had died during the treatment. The complete MR rate after 6 months on blood samples or bone marrow was respectively 83% (43/50) and 74 % (32/43). At 24 months, the PFS was 69% and the OS 80%. The MIPI score (high vs low/int) and the blood MR after 6 cycles were the only two statistically prognostic factors for PFS and OS. Toxicities were essentially hematologic with grade 3 or 4 neutropenia and thrombocytopenia in 51% and 36% of the cases, respectively. The main grade 3 or 4 extra-hematologic toxicities were fatigue (19%), neuropathy (14%), cardiac (7%) or febrile neutropenia (5%). Conclusion: The RiBVD regimen can be safely administered as first line therapy to elderly patients with MCL. Toxicities are mild and manageable. With 74% of CR/CRu, a 2 year PFS of 69% and 86% of patients achieving an MRD negative status in the blood after 6 cycles, without maintenance therapy, the RiBVD regimen is identified as a highly effective, well tolerated, first line treatment for elderly MCL patients. Reference : 1 - Kluin Nelemans HC et al, NEJM 2012, 2 - Gimenez E et al, BJH 2012 Disclosures Gressin: mundipharma: Consultancy. Off Label Use: Bendamustine and Bortezomib did not have authorization to their use in first line for MCL in France. Karlin:Janssen: Honoraria; celgene: Consultancy, Honoraria; Sandoz: Consultancy. Le Gouill:Mundipharma: Honoraria; Roche: Honoraria; Janssen: Consultancy.

Published
2014

47. Intravascular bone marrow accumulation in persistent polyclonal lymphocytosis: a misleading feature for B-cell neoplasm

Author

Pierre Lederlin, Philippe Jonveaux, Véronique Dorvaux, Eric Labouyrie, Anne Kennel De March, Marie José Grégoire, Pierre Feugier, Jean François Lesesve, Nathalie Monhoven, Françoise Braun, and Marie C. Béné

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Lymphocytosis, T cell, Biology, Polymerase Chain Reaction, Pathology and Forensic Medicine, Immunophenotyping, Antigens, CD, Bone Marrow, medicine, Humans, Gene Rearrangement, B-Lymphocytes, Receptors, Antigen, T-Cell, gamma-delta, Gene rearrangement, Middle Aged, medicine.disease, Lymphoma, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, Polyclonal antibodies, Karyotyping, Immunology, Cytogenetic Analysis, biology.protein, Blood Vessels, Female, Bone marrow, medicine.symptom, Clone (B-cell biology), Immunoglobulin Heavy Chains
Abstract

Persistent polyclonal B-cell lymphocytosis is usually reported in young smoking women. Whether this syndrome represents a premalignant or benign disease remains unclear. Indeed, because of the association of Bcl-2/IgH rearrangement and cytogenetic abnormalities, such cases may be misdiagnosed as the leukemic phase of a non-Hodgkin's lymphoma. We report eight new cases of persistent polyclonal B-cell lymphocytosis, which displayed a misleading bone marrow histological pattern, that is, intravascular B-cell infiltrate, constantly associated with Bcl-2 immunohistostaining, as seen in some lymphoma. We also show the absence or low expression of adhesion molecules on persistent polyclonal B-cell lymphocytes, suggesting that migration abnormalities might lead to bone marrow and peripheral blood accumulation. Although most cases presented multiple Bcl-2/IgH gene rearrangements and appeared to be polyclonal, oligoclonal expansion was identified in one out of eight patients, yet was not associated with clinical aggressiveness. The occasional reports of oligoclonal IgH and Bcl-2/IgH rearrangements in this disorder suggest that polyclonal expansion may be followed by the emergence of a predominant clone. However, the benign clinical course and lack of biological evolution in most cases imply that it is mandatory to distinguish this disorder from other malignant lymphoproliferations, so that unnecessary aggressive therapy can be avoided.

Published
2004

48. Septicémie à Yersinia enterocolitica, surcharge ferrique et déféroxamine

Author

P. Lederlin, J.F. Paitel, Véronique Dorvaux, and A Guerci

Subjects
Deferoxamine, biology, business.industry, Immunology, Gastroenterology, Internal Medicine, medicine, bacteria, Yersinia enterocolitica, biology.organism_classification, business, Molecular biology, medicine.drug
Abstract

Resume Les infections a Yersinia enterocolitica sont le plus souvent limitees au tube digestif. Quand celles-ci sont generalisees, une surcharge en fer et surtout un traitement chelateur du fer sont souvent incrimines. Nous rapportons le cas d'un patient âge de 55 ans porteur d'une anemie sideroblastique traitee par transfusions iteratives et deferoxamine depuis 4 ans et arginate d'heme depuis 2 mois, hospitalise pour une septicemie en rapport avec une infection a Yersinia enterocolitica. Le traitement par cephalosporines de troisieme generation et aminosides a permis d'obtenir une evolution favorable de l'episode infectieux.

Published
1995

49. Tolerability of postexposure prophylaxis with zidovudine, lamivudine, and nelfinavir for human immunodeficiency virus infection

Author

Hélène Schuhmacher, Sibylle Bevilacqua, Thierry May, Philippe Canton, Christian Rabaud, Véronique Dorvaux, and Isabelle Beguinot

Subjects
Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, medicine.medical_treatment, education, HIV Infections, Zidovudine, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Medicine, Humans, Prospective Studies, Post-exposure prophylaxis, Adverse effect, Nelfinavir, business.industry, virus diseases, Lamivudine, medicine.disease, Virology, Infectious Diseases, Tolerability, Chemoprophylaxis, cardiovascular system, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, business, medicine.drug
Abstract

Tolerability of the combination of zidovudine, lamivudine, and nelfinavir used as postexposure prophylaxis (PEP) for HIV infection was prospectively evaluated among 185 patients at 11 hospitals in eastern France. After exclusion of the 106 persons who discontinued PEP either because the source patient subsequently tested HIV seronegative or because the injury was reassessed as resulting in a low risk for transmission of HIV, 67 (85%) of the patients who received such PEP experienced adverse effects, which led to withdrawal of nelfinavir in 28 (35%) of these patients.

Published
2000

50. Supériorité confirmée de l’association melphalan-prednisone–thalidomide (MP–T) chez des patients de plus de 75 ans avec un myélome multiple (MM) de novo : protocole IFM 01/01, MP–T versus MP en double insu versus placebo

Author

Eric Voog, Isabelle Azais, M Maigre, Olivier Decaux, J P Eschard, Marc Wetterwald, L. Voillat, C. Hulin, Laurent Garderet, Philippe Rodon, P. Moreau, and Véronique Dorvaux

Subjects
business.industry, Gastroenterology, Internal Medicine, Medicine, business
Published
2008

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