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 Callanan 43, 2
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<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.
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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, Ferrata Storti Foundation, 2018, 104 (1), pp.138-146. ⟨10.3324/haematol.2018.191429⟩. ⟨hal-02265274⟩

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