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

Rémy Gressin (1, 2) , Nicolas Daguindau (3) , Adrian Tempescul (4, 5) , Anne Moreau (6) , Sylvain Carras (1) , Emmanuelle Tchernonog (7) , Anna Schmitt (8) , Roch Houot (9) , Caroline Dartigeas (10) , Jean Michel Pignon (11) , Selim Corm (12) , Anne Banos (13) , Christiane Mounier (14) , Jehan Dupuis (15) , Margaret Macro (16, 17) , Joel Fleury (18) , Fabrice Jardin (19, 20) , Clémentine Sarkozy (21) , Ghandi Damaj (22) , Pierre Feugier (23) , Luc Matthieu Fornecker (24) , Cécile Chabrot (18) , Véronique Dorvaux (25) , Krimo Bouadallah (26) , Sandy Amorin (27) , Reda Garidi (28) , Laurent Voillat (29) , Bertrand Joly (30) , Philippe Solal Celigny (31) , Nadine Morineau (32) , Marie Pierre Moles (33) , Hacène Zerazhi (34, 35) , Jean Fontan (36) , Yazid Arkam (37) , Magda Alexis (38) , Vincent Delwail (39) , Jean Pierre Vilque (40) , Loic Ysebaert (41) , Steven Le Gouill (42) , Mary B. Callanan (43, 2)

1 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
2 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
3 Service d'Hématologie [CH Annecy]
4 CHU-Brest-Hemato - CHRU Brest - Service d'Hématologie
5 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
6 Département de Pathologie [CHU Nantes]
7 Département d'hématologie biologique[Montpellier]
8 Dpt hématologie [CHU Bordeaux]
9 Service d’Hématologie Clinique [Rennes]
10 Département d’Hématologie Clinique [CHU Tours]
11 Service d'hématologie (CH de Dunkerque)
12 Service Hématologie [CH Métropole Savoie, Chambery]
13 Hôpital de Bayonne
14 Service d'Hématologie [ CHU Saint-Etienne]
15 Centre hospitalier universitaire Henri-Mondor [Créteil]
16 Hôpital Universitaire de Caen
17 Laboratoire d'Hématologie Biologique [CHU Caen]
18 Service d’Hématologie Biologique [CHU Clermont-Ferrand]
19 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
20 Département d’Hématologie [Rouen]
21 Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL]
22 Laboratoire d'Hématologie [CHU Amiens]
23 Service d'Hématologie [CHRU Nancy]
24 Département d'Oncologie et Hématologie [Strasbourg]
25 Service d'hématologie [CHR Metz-Thionville]
26 Service d'Hématologie [Bordeaux]
27 IRSL - Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex-Institut Universitaire Hématologie-IUH)
28 Hôpital Saint-Quentin
29 Service d'hématologie et oncologie [Centre Hospitalier de Chalon-sur-Saône William Morey]
30 Hôpital de Corbeil
31 Service d'Oncologie médicale [Clinique Victor Hugo]
32 CCS - Centre Catherine-de-Sienne [Nantes]
33 Département d'Hématologie Clinique [CHU d'Angers]
34 Médecine Interne Onco-hématologie
35 Centre Hospitalier Henri Duffaut (Avignon)
36 Service d'hématologie
37 Service Hématologie, Mulhouse
38 Hématologie Biologique [CHR d'Orléans]
39 Service d’Oncologie Hématologique et Thérapie Cellulaire [CHU Poitiers]
40 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
41 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
42 Service d'Hématologie [Nantes]
43 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand

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<0.0001). Neither the mantle cell lymphoma index, nor fluorodeoxyglucose-positron emission tomography nor Ki67 positivity (cut off of ≥30%) showed a prognostic impact for survival. Hematologic grade 3-4 toxicities were mainly neutropenia (51%), thrombocytopenia (35%) and lymphopenia (65%). Grade 3-4 non-hematologic toxicities were mainly fatigue (18.5%), neuropathy (15%) and infections. In conclusion, the tested treatment regimen is active as frontline therapy in older patients with mantle cell lymphoma, with manageable toxicity. Minimal residual disease status after induction could serve as an early predictor of survival in mantle cell lymphoma. ClinicalTrials.gov: NCT 01457144.

Domaines: Immunologie

Rémy Gressin, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Sylvain Carras, et al.. A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma. Haematologica, 2018, 104 (1), pp.138-146. ⟨10.3324/haematol.2018.191429⟩. ⟨hal-02265274⟩