Lenalidomide, bendamustine, and rituximab as first-line therapy for patients > 65 years with mantle cell lymphoma: The Nordic Lymphoma Group MCL4 (LENA-BERIT) trial.

Abstract

e18567 Background: Mantle cell lymphoma is a disease of the elderly, with a median age of 70 years. Younger patients may be treated with potentially curative treatment including high dose chemotherapy. (Geisler CH. Blood. 2008;12:2687-93.) For elderly patients, however, no standard therapy has been defined. In a randomized comparison between R-CHOP and R-bendamustine (R-B) by the German StiL Group, R-B was associated with less toxicity and improved outcome, making R-B the preferable first-line therapy. (Rummel, M.J, American Society of Hematology. 2009: New Orleans, Abstract 405.) Lenalidomide is another active agent in MCL, with a response rate of 53% in relapsed/refractory MCL. (Wiernik, P.H, J Clin Oncol. 2008;26:4952-7.) In the current trial, we investigate if the addition of lenalidomide to R-B may enhance efficacy, with manageable toxicity, for the older population of MCL patients. Methods: In phase I, the MTD of lenalidomide will be determined, starting with 5 mg/day given up to 25 mg/day in sequential dose escalation by a 3+3 design. Additional subjects are enrolled at the MTD on the phase II portion, up to a total number of 60 patients. Lenalidomide, bendamustine and rituximab are given in 6 cycles/28 days. Lenalidomide D1-21, bendamustine 90 mg/m2 D1-2 and rituximab 375 mg/m2 D1. The maintenance phase, consists of lenalidomide 25 mg/day, D1-21, for 7 cycles. Eligibility criteria are age > 65 years, or ≤ 65 years, unable to tolerate high dose chemotherapy, with untreated mantle cell lymphoma, stage II-IV. Results: The trial was commenced in October 2009, and will recruit patients from an initial 17 centres in Sweden, Norway and Denmark. Centres in Finland will be activated at a later stage. The planned study duration is 2 years. Conclusions: A prolongation of median PFS with 6 months compared to the R-B arm in the StiL study is considered clinically significant, meriting further study of the LBR regimen in a phase III setting. In a preliminary analysis of the STiL study, the median PFS for patients with MCL in the R-B arm is 30 months, indicating that a median PFS of ≥ 36 months with the LBR regimen would be a clinically significant improvement. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene