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19 results on '"for the Lymphoma Study Association"'

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

Author

Rémy Gressin, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Sylvain Carras, Emmanuelle Tchernonog, Anna Schmitt, Roch Houot, Caroline Dartigeas, Jean Michel Pignon, Selim Corm, Anne Banos, Christiane Mounier, Jehan Dupuis, Margaret Macro, Joel Fleury, Fabrice Jardin, Clementine Sarkozy, Ghandi Damaj, Pierre Feugier, Luc Matthieu Fornecker, Cecile Chabrot, Veronique Dorvaux, Krimo Bouadallah, Sandy Amorin, Reda Garidi, Laurent Voillat, Bertrand Joly, Philippe Solal Celigny, Nadine Morineau, Marie Pierre Moles, Hacene Zerazhi, Jean Fontan, Yazid Arkam, Magda Alexis, Vincent Delwail, Jean Pierre Vilque, Loic Ysebaert, Steven Le Gouill, Mary B. Callanan, and for the Lymphoma Study Association

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

We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (P

Published
2019
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4. International Extranodal NK/T-cell Lymphoma Project (PINK)

Author

Seok Jin Kim, Consortium for Improving Survival of Lymphoma, Asia Lymphoma Study Group, Lymphoma Study Association, Dok Hyun Yoon, Arnaud Jaccard, Wee Joo Chng, Soon Thye Lim, Huangming Hong, Yong Park, Kian Meng Chang, Yoshinobu Maeda, Fumihiro Ishida, Dong-Yeop Shin, Jin Seok Kim, Seong Hyun Jeong, Deok-Hwan Yang, Jae-Cheol Jo, Gyeong-Won Lee, Chul Won Choi, Won-Sik Lee, Tsai-Yun Chen, Kiyeun Kim, Sin-Ho Jung, Tohru Murayama, Yasuhiro Oki, Ranjana Advani, Francesco d'Amore, Norbert Schmitz, Cheolwon Suh, Ritsuro Suzuki, Yok Lam Kwong, Tong-Yu Lin, and Won Seog Kim, Professor

Published
2017

10. Central nervous system relapse in patients over 80 years with diffuse large B-cell lymphoma: an analysis of two LYSA studies

Author

Cabannes‐Hamy, Aurélie, Peyrade, Frederic, Jardin, Fabrice, Emile, Jean‐François, Delwail, Vincent, Mounier, Nicolas, Haioun, Corinne, Perrot, Aurore, Fitoussi, Olivier, Lara, Diane, Delarue, Richard, André, Marc, Offner, Fritz, Ghesquières, Hervé, Pascal, Laurent, Soussain, Carole, Lazarovici, Julien, Schiano, Jean-Marc, Gaulard, Philippe, Tilly, Hervé, Thieblemont, Catherine, LYSA (LYmphoma Study Association), Bosly, André, Van Den Neste, Eric, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), 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), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, 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), Service d’Oncologie Hématologique et Thérapie Cellulaire [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Polyclinique Bordeaux Nord Aquitaine, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de Recherche d'Histoire (GRHis), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Universiteit Gent = Ghent University [Belgium] (UGENT), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CRLCC René Huguenin, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), 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, École normale supérieure - Lyon (ENS 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), Polyclinique Bordeaux Nord Aquitaine (PBNA), Universiteit Gent = Ghent University (UGENT), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Laboratoire épidémiologie et oncogénèse des tumeurs digestives, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Ghent University [Belgium] (UGENT), Université de Lille, CHU Lille, UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, and UCL - (SLuc) Service d'hématologie

Subjects
Male, Cancer Research, CHOP CHEMOTHERAPY, [SDV]Life Sciences [q-bio], Aggressive lymphoma, Central Nervous System Neoplasms, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, Medicine and Health Sciences, SINGLE-ARM, Medicine, Cumulative incidence, ELDERLY-PATIENTS, ComputingMilieux_MISCELLANEOUS, Original Research, CNS relapse, Aged, 80 and over, education.field_of_study, Incidence (epidemiology), 3. Good health, CNS PROPHYLAXIS, Oncology, 030220 oncology & carcinogenesis, Female, Rituximab, Lymphoma, Large B-Cell, Diffuse, medicine.drug, medicine.medical_specialty, Population, PHASE-2 TRIAL, Ofatumumab, elderly, STUDY-GROUP DSHNHL, 03 medical and health sciences, Internal medicine, Humans, Radiology, Nuclear Medicine and imaging, NON-HODGKINS-LYMPHOMA, education, Aged, Retrospective Studies, AGGRESSIVE LYMPHOMA, business.industry, Clinical Cancer Research, Retrospective cohort study, medicine.disease, chemistry, Aged 80 and over, RITUXIMAB ERA, DLBCL, RISK-FACTORS, business, Diffuse large B-cell lymphoma, 030215 immunology
Abstract

CNS relapse is reported in 2–5% of diffuse large B‐cell lymphoma (DLBCL) patients, dramatically decreasing overall survival (OS). Very few studies address incidence and risk factors of CNS relapse in very elderly patients, a challenging population to treat given their commonly associated comorbidities. A retrospective analysis was performed of 270 DLBCL patients >80 years treated between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03‐7B, LNH09‐7B) evaluating the addition of rituximab or ofatumumab to mini‐CHOP as front‐line therapy. No patients received CNS prophylaxis. CNS relapse was evaluated according to cumulative incidence, patient characteristics, risk factors, and survival. Median age was 83 years (range: 79–95). After a median follow‐up of 28.7 months, eight patients had CNS relapse (3.0%). Median time between inclusion and CNS relapse was 19.2 months (range: 3.2–32.6). Patients survived a median of 1.5 months after CNS relapse (range: 0.4–4.1). Median OS from relapse was significantly lower in CNS relapse patients (1.5 months, 95% CI: 0.4–3.5) compared to patients with non‐CNS relapse (6.6 months; 95% CI: 4.6–11.9). No baseline characteristics were associated with CNS relapse. The proportion of patients with CNS disease did not differ significantly between patients with low‐intermediate risk according to CNS‐IPI and patients with high risk (3% vs. 2.8%, P = 1.00). CNS relapse cumulative incidence in very elderly treatment‐naive patients is 1.8% at 2 years and is associated with poor survival. This population had a long median time to CNS relapse. Absence of prophylaxis did not strongly impact CNS relapse incidence.

Published
2018

11. Bendamustine and rituximab in elderly patients with low-tumour burden follicular lymphoma. Results of the LYSA phase II BRIEF study

Author

Gyan, Emmanuel, Sonet, Anne, Brice, Pauline, Anglaret, Bruno, Laribi, Kamel, Fruchart, Christophe, Tilly, Hervé, Araujo, Carla, Soubeyran, Pierre, Gonzalez, Hugo, Morineau, Nadine, Nicolas-Virelizier, Emmanuelle, Ghesquières, Hervé, Salles, Bruno, Bouabdallah, Réda, Orfeuvre, Hubert, Fahri, Jonathan, Couturier, Olivier, Xerri, Luc, Feugier, Pierre, Lymphoma Study Association (LYSA), Service d'hématologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Catholique de Louvain = Catholic University of Louvain (UCL), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Valence (Unité d'Hématologie), Centre hospitalier de Valence, Centre Hospitalier Le Mans (CH Le Mans), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, 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), Service d'hématologie (CH de la Côte Basque), Le CHCB, Centre Hospitalier de la Côte Basque, Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Catherine-de-Sienne [Nantes] (CCS), Centre Léon Bérard [Lyon], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier de Bourg en Bresse, Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), 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)-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), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie

Subjects
Bendamustine, Male, medicine.medical_specialty, Efficacy, [SDV]Life Sciences [q-bio], efficacy, Follicular lymphoma, Phases of clinical research, Gastroenterology, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, rituximab, Maintenance therapy, follicular lymphoma, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Bendamustine Hydrochloride, Humans, bendamustine, Lymphoma, Follicular, Aged, Aged, 80 and over, tolerance, business.industry, Remission Induction, Hematology, Middle Aged, medicine.disease, Survival Analysis, 3. Good health, Lymphoma, Tumor Burden, Regimen, Treatment Outcome, 030220 oncology & carcinogenesis, Rituximab, Female, business, Tolerance, 030215 immunology, medicine.drug
Abstract

International audience; The treatment of low-tumour burden follicular lymphoma (LTBFL) remains a challenge. Rituximab-based strategies may be improved by adding chemotherapy. This Lymphoma Study Association multicentre phase II study assessed rituximab and bendamustine in 63 patients with untreated LTBFL who were aged over 60years old and had a follicular lymphoma International Prognostic Index (FLIPI) score ≥2. Induction comprised 4 weekly cycles of rituximab 375mg/m intravenously combined with 2 cycles of bendamustine 90mg/m days 1-2 with a 28-day interval, followed by twelve cycles of 375mg/m rituximab maintenance therapy every 8weeks. The primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12weeks. Median age was 67·4years and median FLIPI was 3. Ultimately, 18 patients (29%) had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires criteria. The 12-week CR/CRu rate was 54·0% and the overall response rate was 93·7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm). Progression-free survival was 85·4% at 24months. In LTBFL patients with FLIPI ≥2, two cycles of rituximab and bendamustine result in a CR rate of 54·0%. However, the treatment-related deaths observed do not allow this regimen to be recommended for LTBFL patients aged over 60years. EudraCT: 2010-020757-14; ClinicalTrials.gov: NCT01313611.

Published
2018

12. Central nervous system relapse in patients over 80 years with diffuse large B-cell lymphoma: an analysis of two LYSA studies.

Author

UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Service d'hématologie, Cabannes‐Hamy, Aurélie, Peyrade, Frederic, Jardin, Fabrice, Emile, Jean‐François, Delwail, Vincent, Mounier, Nicolas, Haioun, Corinne, Perrot, Aurore, Fitoussi, Olivier, Lara, Diane, Delarue, Richard, André, Marc, Offner, Fritz, Ghesquières, Hervé, Pascal, Laurent, Soussain, Carole, Lazarovici, Julien, Schiano, Jean-Marc, Gaulard, Philippe, Tilly, Hervé, Thieblemont, Catherine, LYSA (LYmphoma Study Association), Bosly, André, Van Den Neste, Eric, UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Service d'hématologie, Cabannes‐Hamy, Aurélie, Peyrade, Frederic, Jardin, Fabrice, Emile, Jean‐François, Delwail, Vincent, Mounier, Nicolas, Haioun, Corinne, Perrot, Aurore, Fitoussi, Olivier, Lara, Diane, Delarue, Richard, André, Marc, Offner, Fritz, Ghesquières, Hervé, Pascal, Laurent, Soussain, Carole, Lazarovici, Julien, Schiano, Jean-Marc, Gaulard, Philippe, Tilly, Hervé, Thieblemont, Catherine, LYSA (LYmphoma Study Association), Bosly, André, and Van Den Neste, Eric

Abstract

CNS relapse is reported in 2-5% of diffuse large B-cell lymphoma (DLBCL) patients, dramatically decreasing overall survival (OS). Very few studies address incidence and risk factors of CNS relapse in very elderly patients, a challenging population to treat given their commonly associated comorbidities. A retrospective analysis was performed of 270 DLBCL patients >80 years treated between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03-7B, LNH09-7B) evaluating the addition of rituximab or ofatumumab to mini-CHOP as front-line therapy. No patients received CNS prophylaxis. CNS relapse was evaluated according to cumulative incidence, patient characteristics, risk factors, and survival. Median age was 83 years (range: 79-95). After a median follow-up of 28.7 months, eight patients had CNS relapse (3.0%). Median time between inclusion and CNS relapse was 19.2 months (range: 3.2-32.6). Patients survived a median of 1.5 months after CNS relapse (range: 0.4-4.1). Median OS from relapse was significantly lower in CNS relapse patients (1.5 months, 95% CI: 0.4-3.5) compared to patients with non-CNS relapse (6.6 months; 95% CI: 4.6-11.9). No baseline characteristics were associated with CNS relapse. The proportion of patients with CNS disease did not differ significantly between patients with low-intermediate risk according to CNS-IPI and patients with high risk (3% vs. 2.8%, P = 1.00). CNS relapse cumulative incidence in very elderly treatment-naive patients is 1.8% at 2 years and is associated with poor survival. This population had a long median time to CNS relapse. Absence of prophylaxis did not strongly impact CNS relapse incidence.

Published
2018

13. Bendamustine and rituximab in elderly patients with low-tumour burden follicular lymphoma. Results of the LYSA phase II BRIEF study.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Gyan, Emmanuel, Sonet, Anne, Brice, Pauline, Anglaret, Bruno, Laribi, Kamel, Fruchart, Christophe, Tilly, Hervé, Araujo, Carla, Soubeyran, Pierre, Gonzalez, Hugo, Morineau, Nadine, Nicolas-Virelizier, Emmanuelle, Ghesquières, Hervé, Salles, Bruno, Bouabdallah, Réda, Orfeuvre, Hubert, Fahri, Jonathan, Couturier, Olivier, Xerri, Luc, Feugier, Pierre, Lymphoma Study Association (LYSA), UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Gyan, Emmanuel, Sonet, Anne, Brice, Pauline, Anglaret, Bruno, Laribi, Kamel, Fruchart, Christophe, Tilly, Hervé, Araujo, Carla, Soubeyran, Pierre, Gonzalez, Hugo, Morineau, Nadine, Nicolas-Virelizier, Emmanuelle, Ghesquières, Hervé, Salles, Bruno, Bouabdallah, Réda, Orfeuvre, Hubert, Fahri, Jonathan, Couturier, Olivier, Xerri, Luc, Feugier, Pierre, and Lymphoma Study Association (LYSA)

Abstract

The treatment of low-tumour burden follicular lymphoma (LTBFL) remains a challenge. Rituximab-based strategies may be improved by adding chemotherapy. This Lymphoma Study Association multicentre phase II study assessed rituximab and bendamustine in 63 patients with untreated LTBFL who were aged over 60 years old and had a follicular lymphoma International Prognostic Index (FLIPI) score ≥2. Induction comprised 4 weekly cycles of rituximab 375 mg/m intravenously combined with 2 cycles of bendamustine 90 mg/m days 1-2 with a 28-day interval, followed by twelve cycles of 375 mg/m rituximab maintenance therapy every 8 weeks. The primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12 weeks. Median age was 67·4 years and median FLIPI was 3. Ultimately, 18 patients (29%) had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires criteria. The 12-week CR/CRu rate was 54·0% and the overall response rate was 93·7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm). Progression-free survival was 85·4% at 24 months. In LTBFL patients with FLIPI ≥2, two cycles of rituximab and bendamustine result in a CR rate of 54·0%. However, the treatment-related deaths observed do not allow this regimen to be recommended for LTBFL patients aged over 60 years. EudraCT: 2010-020757-14; ClinicalTrials.gov: NCT01313611.

Published
2018

14. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification.

Author

Cheson, Bruce D, Fisher, Richard I, Barrington, Sally F, Cavalli, Franco, Schwartz, Lawrence H, Lister, T Andrew, Alliance, Australasian Leukaemia and Lymphoma Group, Zucca, Emanuele, Eastern Cooperative Oncology Group, European Mantle Cell Lymphoma Consortium, Italian Lymphoma Foundation, European Organisation for Research, Treatment of Cancer/Dutch Hemato-Oncology Group, Grupo Español de Médula Ósea, German High-Grade Lymphoma Study Group, German Hodgkin's Study Group, Japanese Lymphorra Study Group, Lymphoma Study Association, NCIC Clinical Trials Group, and Nordic Lymphoma Study Group

Published
2014
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15. Central nervous system relapse in patients over 80 years with diffuse large B‐cell lymphoma: an analysis of two LYSA studies

Author

Aurélie Cabannes‐Hamy, Frederic Peyrade, Fabrice Jardin, Jean‐François Emile, Vincent Delwail, Nicolas Mounier, Corinne Haioun, Aurore Perrot, Olivier Fitoussi, Diane Lara, Richard Delarue, Marc André, Fritz Offner, Hervé Ghesquières, Laurent Pascal, Carole Soussain, Julien Lazarovici, Jean‐Marc Schiano, Philippe Gaulard, Hervé Tilly, Catherine Thieblemont, the LYSA, and the lymphoma study association

Subjects
Aged 80 and over, CNS relapse, DLBCL, elderly, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract CNS relapse is reported in 2–5% of diffuse large B‐cell lymphoma (DLBCL) patients, dramatically decreasing overall survival (OS). Very few studies address incidence and risk factors of CNS relapse in very elderly patients, a challenging population to treat given their commonly associated comorbidities. A retrospective analysis was performed of 270 DLBCL patients >80 years treated between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03‐7B, LNH09‐7B) evaluating the addition of rituximab or ofatumumab to mini‐CHOP as front‐line therapy. No patients received CNS prophylaxis. CNS relapse was evaluated according to cumulative incidence, patient characteristics, risk factors, and survival. Median age was 83 years (range: 79–95). After a median follow‐up of 28.7 months, eight patients had CNS relapse (3.0%). Median time between inclusion and CNS relapse was 19.2 months (range: 3.2–32.6). Patients survived a median of 1.5 months after CNS relapse (range: 0.4–4.1). Median OS from relapse was significantly lower in CNS relapse patients (1.5 months, 95% CI: 0.4–3.5) compared to patients with non‐CNS relapse (6.6 months; 95% CI: 4.6–11.9). No baseline characteristics were associated with CNS relapse. The proportion of patients with CNS disease did not differ significantly between patients with low‐intermediate risk according to CNS‐IPI and patients with high risk (3% vs. 2.8%, P = 1.00). CNS relapse cumulative incidence in very elderly treatment‐naive patients is 1.8% at 2 years and is associated with poor survival. This population had a long median time to CNS relapse. Absence of prophylaxis did not strongly impact CNS relapse incidence.

Published
2018
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16. Soluble programmed death-ligand 1 as a prognostic biomarker for overall survival in patients with diffuse large B-cell lymphoma: a replication study and combined analysis of 508 patients

Author

Karin Tarte, Thomas E. Witzig, Imane Azzaoui, Thomas M. Habermann, Andrew L. Feldman, Céline Pangault, Noel Milpied, Stephen M. Ansell, Thierry Fest, Marie Parrens, Matthew J. Maurer, James R. Cerhan, Delphine Rossille, Mikael Roussel, Susan L. Slager, Thierry Lamy, Gaëlle Labouré, Brian K. Link, 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], Mayo Clinic [Rochester], CHU Bordeaux [Bordeaux], University of Iowa [Iowa City], This study is supported by the French Health Minister (BMS_LyTrans project, NCT01287923), the National Institute of Cancer (INCa Translational Research 2010), the French Lymphoma Study Association (LYSA), the French National Agency for Research (ANR Carnot/CALYM), the National Cancer Institute (P50 CA97274, R01 CA92153), and the Henry J Predolin Foundation. Concerning the French cohort, we are indebted to the LYSA pathology platform (Hôpital Henri Mondor, Créteil) for immunohistochemical experiments, the Centre de Ressources Biologiques CRB-Santé (BB-0033-00056) of the Rennes hospital for providing high quality samples. This work was partly supported by a French National Cancer Institute post-doctoral fellowship (grant number PDOC-RC-GO/07-003) to the first author (D.R.)., 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 ), and Chard-Hutchinson, Xavier

Subjects
Adult, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, medicine.medical_specialty, Adolescent, Programmed Cell Death 1 Receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Refractory, immune system diseases, hemic and lymphatic diseases, Internal medicine, Biomarkers, Tumor, Tumor Microenvironment, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Hematology, business.industry, Peripheral tolerance, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, Prognosis, medicine.disease, 3. Good health, Lymphoma, Leukemia, Oncology, Apoptosis, 030220 oncology & carcinogenesis, Immunology, Cancer research, Female, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, 030215 immunology, medicine.drug
Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematologic malignancy with more than two-thirds of the patients cured with first-line rituximab-based treatments. However, relapsing or refractory patients have a very poor survival despite salvage therapies. The PD-1/PD-L1 pathway plays a major role in peripheral tolerance and homeostasis by inhibiting T-cell activation.

Published
2017

17. Total metabolic tumor volume, circulating tumor cells, cell-free DNA: distinct prognostic value in follicular lymphoma

Author

Axel Van Der Gucht, Jehan Dupuis, E. Itti, René-Olivier Casasnovas, Philippine Robert, Alina Berriolo-Riedinger, Salma Hamdane, Jean-Philippe Jais, Asma Beldi-Ferchiou, Gaelle Laboure, Christiane Copie-Bergman, Benjamin Verret, Marie-Hélène Delfau-Larue, Ichrafe Benmaad, Isabelle Nel, Corinne Haioun, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, The lymphoma study association (LYSA), CHU Henri Mondor, Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] (CGFL), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), 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), Service de médecine nucléaire [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and 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

Subjects
Adult, Male, 0301 basic medicine, Oncology, endocrine system, medicine.medical_specialty, Follicular lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Polymerase Chain Reaction, Circulating Tumor DNA, law.invention, 03 medical and health sciences, 0302 clinical medicine, Circulating tumor cell, immune system diseases, Predictive Value of Tests, law, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Digital polymerase chain reaction, Lymphoma, Follicular, Polymerase chain reaction, Survival analysis, Aged, Retrospective Studies, Lymphoid Neoplasia, business.industry, Hematology, Middle Aged, Neoplastic Cells, Circulating, Prognosis, medicine.disease, Survival Analysis, Tumor Burden, 3. Good health, Lymphoma, 030104 developmental biology, Cell-free fetal DNA, 030220 oncology & carcinogenesis, Predictive value of tests, Female, business
Abstract

International audience; Outcomes for follicular lymphoma (FL) have greatly improved, but most patients will ultimately relapse. High total metabolic tumor volume (TMTV), computed from baseline 18F-fluorodeoxyglucose-positron emission tomography (PET), is associated with shorter progression-free survival (PFS), but circulating tumor cells (CTCs) and cell-free DNA (cfDNA) may also reflect tumor burden and be of prognostic value. The aim of our study was to correlate CTCs and cfDNA with TMTV in FL at diagnosis and to determine their prognostic values. We retrospectively analyzed 133 patients (with previously untreated FL and a baseline PET) from 2 cohorts with either a baseline plasma sample (n = 61) or a bcl2-JH-informative peripheral blood (PB) sample (n = 68). Quantification of circulating bcl2-JH+ cells and cfDNA was performed by droplet digital polymerase chain reaction. A significant correlation was found between TMTV and both CTCs (P < .0001) and cfDNA (P < .0001). With a median 48-month follow-up, 4-year PFS was lower in patients with TMTV > 510 cm3 (P = .0004), CTCs >0.0018 PB cells (P = .03), or cfDNA >2550 equivalent-genome/mL (P = .04). In comparison with TMTV alone, no additional prognostic information was obtained by measuring CTCs. In contrast, Cox multivariate analysis, including cfDNA and TMTV, showed that both cfDNA and TMTV remained predictive of outcome. In conclusion, CTCs and cfDNA correlate with TMTV in FL, and all 3 influence patient outcome. PFS was shorter for patients with high cfDNA and TMTV, suggesting that these parameters provide relevant information for tumor-tailored therapy.

Published
2018

18. Regulatory myeloid cells: an underexplored continent in B-cell lymphomas

Author

Cédric Ménard, Jonathan M. Irish, Karin Tarte, Thierry Fest, Mikael Roussel, Faustine Lhomme, Jonchère, Laurent, Etablissement français du sang [Rennes] (EFS Bretagne), Service d’immunologie, de thérapie cellulaire et d’hématopoïèse, Hôpital Pontchaillou, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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 ), Vanderbilt University School of Medicine [Nashville], CHU Pontchaillou [Rennes], This work was supported by a research grant from the National Institute of Cancer (INCa Recherche Translationnelle 2010), Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang (GOELAMS), LYSA group (Lymphoma Study Association), Comité pour la Recherche Clinique et Translationnelle (CORECT, CHU Rennes), Ligue Nationale Contre le Cancer, R00 CA143231-03, the Vanderbilt-Ingram Cancer Center (VICC, P30 CA68485), VICC Ambassadors, and a VICC Hematology Helping Hands award., Université de Rennes 1 (UR1), and 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 )

Subjects
0301 basic medicine, Cancer Research, Lymphoma, B-Cell, Myeloid, [SDV.IMM] Life Sciences [q-bio]/Immunology, Carcinogenesis, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Tumor-associated macrophage, Biology, Immunomodulation, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, Regulatory myeloid suppressor cells, medicine, Myeloid-derived suppressor cell, Animals, Humans, Immunology and Allergy, B-cell lymphoma, B cell, Tumor microenvironment, Myeloid-Derived Suppressor Cells, Germinal center, Germinal Center, medicine.disease, 3. Good health, Lymphoma, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, Oncology, Myeloid-derived Suppressor Cell, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor Escape, Mass cytometry
Abstract

International audience; In lymphomas arising from the germinal center, prognostic factors are linked to the myeloid compartment. In particular, high circulating monocyte or myeloid-derived suppressor cell counts are associated with poor prognosis for patients with high-grade B-cell lymphomas. Macrophages with an M2 phenotype are enriched within lymphoma tumors. However, the M1/M2 nomenclature is now deprecated and the clinical impact of this phenotype remains controversial. Across cancer types, myeloid cells are primarily thought to function as immune suppressors during tumor initiation and maintenance, but the biological mechanisms behind the myeloid signatures are still poorly understood in germinal center B-cell lymphomas. Herein, we describe the role and clinical relevance of myeloid cells in B-cell lymphoma and propose innovative approaches to decipher this complex cellular compartment. Indeed, characterization of this heterogeneous cell ecosystem has been largely accomplished with "low-resolution" approaches like morphological evaluation and immunohistochemistry, where cells are characterized using a few proteins and qualitative metrics. High-resolution, quantitative approaches, such as mass cytometry, are valuable to better understand myeloid cell diversity, functions, and to identify potential targets for novel therapies.

Published
2017

19. T-cell defect in Diffuse Large B-cell Lymphomas involves expansion of myeloid derived suppressor cells expressing IL-10, PD-L1 and S100A12

Author

Azzaoui, Imane, Uhel, Fabrice, Rossille, Delphine, Pangault, Celine, Dulong, Joelle, Le Priol, Jerome, Lamy, Thierry, Houot, Roch, Le Gouill, Steven, Cartron, Guillaume, Godmer, Pascal, Bouabdallah, Krimo, Milpied, Noel, Damaj, Gandhi, Tarte, Karin, Fest, Thierry, Roussel, Mikael, CHU Pontchaillou [Rennes], Etablissement français du sang [Rennes] (EFS Bretagne), Microenvironnement et cancer (MiCa), 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 ), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CHU Bordeaux [Bordeaux], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), This work was supported by a research grant from the National Institute of Cancer (INCa Recherche Translationnelle 2010), the Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang, the Lymphoma Study Association (LYSA) group, and the Ligue Nationale Contre le Cancer (équipe labellisée). M.R. is a recipient of a fellowship from the Nuovo-Soldati Fundation., Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Jonchère, Laurent, Université de Rennes 1 (UR1), and 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 )

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, hemic and lymphatic diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

International audience; In diffuse large B-cell lymphoma (DLBCL), the number of circulating monocytes and neutrophils represents an independent prognostic factor. These cell subsets include monocytic and granulocytic myeloid-derived suppressor cells (M- and G-MDSCs) defined by their ability to suppress T-cell responses. MDSCs are a heterogeneous population described in inflammatory and infectious diseases and in numerous tumors including multiple myeloma, chronic lymphocytic leukemia, and DLBCL. However, their mechanisms of action remain unclear. We broadly assessed the presence and mechanisms of suppression of MDSC subsets in DLBCL. First, a myeloid suppressive signature was identified by gene expression profiling in DLBCL peripheral blood. Accordingly, we identified, in a cohort of 66 DLBCL patients, an increase in circulating G-MDSC (LinnegHLA-DRnegCD33posCD11bpos) and M-MDSC (CD14posHLA-DRlow) counts. Interestingly, only M-MDSC number was correlated with the International Prognostic Index, event-free survival, and number of circulating Tregs. Furthermore, T-cell proliferation was restored after monocyte depletion. Myeloid-dependent T-cell suppression was attributed to a release of interleukin-10 and S100A12 and increased PD-L1 expression. In summary, we identified expanded MDSC subsets in DLBCL, as well as new mechanisms of immunosuppression in DLBCL.

Published
2016

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