MCL‐R2 ELDERLY: A PHASE III STUDY OF THE  EUROPEAN MCL NETWORK  ASSESSING EFFICACY OF ALTERNATING IMMUNOCHEMOTHERAPY (R‐CHOP / R‐HAD) AND a RITUXIMAB‐LENALIDOMIDE MAINTENANCE

Abstract

Background: In prior studies, we have established a cytarabine-containing induction regimen as the standard approach in younger MCL patients (Hermine, Lancet 2016) whereas rituximab maintenance has improved survival rates both in older patients (Kluin-Nelemans, NEJM 2012) and younger patients after autologous stem cell transplantation (Le Gouill, ASH 2016). In addition, a recent phase II study suggested high efficacy with a rituximab-lenalidomide (R2) combination (Ruan, NEJM 2015). Methods: The MCL-R2 Elderly trial is a phase III study of theEuropean MCL network comparing 8 cycles of R-CHOP versus an alternating induction (3 cycles of R-CHOP / 3 cycles of R-HAD) in older MCL patients followed by combined maintenance (R2) vs. rituximab alone in patients responding to induction.The primary endpoint of the trial is to evaluate whether the addition of lenalidomide to standard rituximab-maintenance improves outcome compared to standard rituximab maintenance after response to induction chemotherapy. Secondary endpoints include overall survival, response rate according to IWG criteria and other efficacy parameters, safety, and MRD (minimal residual disease). For induction, randomization is stratified according to country and MIPI and for maintenance additionally according to type of, and response to, induction.Key inclusion criteria are patient >=60 years of age with untreated MCL ineligible for autologous transplant, but fit enough to tolerate the R-HAD therapy, Ann-Arbor stage II-IV and ECOG PS 0-2. Key exclusion criteria are poor renal, hepatic, or bone marrow functions unless related to lymphoma, HIV, HCV positivity, active HBV infection, poor cardiac function, CNS involvement by lymphoma, contraindication for medical DVT prophylaxis, and prior other malignancies if not disease-free for >=5 years. Evaluation including detection of MRD is performed after cycle 4 of induction, at the end of induction treatment, every 6 months during maintenance and follow-up. A maximum number of 633 subjects will be randomized for induction and 443 for maintenance. Results: Since November 2013, 285 patients have-been included, with France, Belgium, Germany, Netherlands, Portugal, and Spain currently recruiting and Poland being initiated within the next weeks. So far, 178 patients have been randomized for the maintenance part which is in line with the expected number of patients. At least one MRD sample has been collected from 212 of 263 cases (81%). An IDMC will regularly review safety issue and especially secondary primary malignancies. So far, the IDMC has analyzed the clinical course of the first 60 patients randomized for maintenance with 25 patients receiving lenalidomide maintenance for more than 6 months and recommended continuation of the study without any safety concerns. Conclusion: The study is ongoing and open for inclusions with an accrual rate that correspond to our hypothesis.