Biweekly Bendamustine Monotherapy for Relapsed or Refractory Indolent B-Cell Non-Hodgkin Lymphoma and Mantle Cell Lymphoma: A Rabbit-14 Trial

[Background] Bendamustine has demonstrated high response rates in non-Hodgkin lymphomas (NHL). However, standard administration schedule frequently shows delayed hematological recovery resulting in the discontinuation of treatment. Here we designed a novel treatment schedule that could be more tolerable and conducted randomized phase II study (UMIN000008702). [Methods] Patients (pts) with relapsed/refractory(R/R) indolent B-cell NHL and mantle cell lymphoma were randomly assigned to standard arm (120mg/m2 on day1 and 2, every 3 weeks) or Benda-14 arm (120 mg/m2 on day1 and 15, every 4 weeks) of bendamustine monotherapy. Each arm was repeated to 6 cycles and the accomplishment rate (AR) of all scheduled treatment was analyzed as primary end point. [Results] A total of 46 pts were enrolled into the study. Baseline characteristics were: median age 64 years (range 46-78); 48% male; 76% follicular lymphoma; 33% ECOG PS ≥1; 50% having one previous regimen. 65% stage III/IV. 24% bone marrow positive. 33% with bulky mass (>6cm). Using random allocation, twenty two and 24 pts were assigned to standard and Benda-14 arm and the AR of 6 cycles in each arm was 41 and 38%, respectively. The median number of cycles was 4.5 in both arms. Eleven (50%) in standard and 10 (42%) in Benda-14 arm withdrew from protocol due to mainly prolonged hematological toxicities. Three withdrew due to disease progression. Two withdrew due to adverse events (AE). Grade 4 non-hematological AE was observed in one. Overall response rate (ORR) in the standard arm was 77% (95% confidence interval [CI], 59 to 95), including a 50% complete response (CR) compared with 83% (95% CI, 68-99), including a 46% CR in Benda-14 arm. After a median follow-up time of 16 months, the median event-free survival (EFS) in the standard arm and Benda-14 arm was 14.6 months (95% CI, 8-26) and 15 months (95% CI, 11 - not reached), respectively. There was no significant difference between two arms in AR and in EFS (p=0.431). The overall survival (OS) in both arms was the same of 89% at 15 months. [Conclusions] Although this study did not confirm the superiority of Benda-14 to complete 6 cycles of treatment, Benda-14 arm appears to be equally tolerable and active as the present standard therapy. Benda-14 could be a study arm of next trial that determines better practical strategy for this disease population. Disclosures Igarashi: Zenyaku-Kogyo Inc.: Research Funding. Tsukasaki:Daiichi Sankyo Co., Ltd.: Consultancy; Takeda: Research Funding.