Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study

Abstract

MABLE investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabine-ineligible patients with chronic lymphocytic leukemia. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every four weeks for six cycles. Rituximab plus chlorambucil-treated patients without a complete response after Cycle 6 received chlorambucil monotherapy for at least six additional cycles or until complete response. The primary endpoint was complete response rate (confirmed by bone marrow biopsy) after Cycle 6 in first-line patients. Secondary endpoints included progression-free survival, overall survival, minimal residual disease, and safety. Overall, 357 patients were randomized (rituximab plus bendamustine, n=178; rituximab plus chlorambucil, n=179; intent-to-treat population), including 241 first-line patients (n=121 and n=120, respectively); 355 patients received treatment (n=177 and n=178, respectively; safety population). In first-line patients, complete response rate after Cycle 6 (rituximab plus bendamustine, 24%; rituximab plus chlorambucil, 9%; P=0.002) and median progression-free survival (rituximab plus bendamustine, 40 months; rituximab plus chlorambucil, 30 months; P=0.003) were higher with rituximab plus bendamustine than rituximab plus chlorambucil. Overall response rate and overall survival were not different. In first-line patients with a complete response, minimal residual disease-negativity was higher with rituximab plus bendamustine than rituximab plus chlorambucil (66% vs. 36%). Overall adverse event incidence was similar (rituximab plus bendamustine, 98%; rituximab plus chlorambucil, 97%). Rituximab plus bendamustine may be a valuable first-line option for fludarabine-ineligible patients with chronic lymphocytic leukemia.

NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 1.2017

“…8 The median PFS was significantly longer in BR group than in the R-chlorambucil group (40 vs 30 months; P=.003), but the median OS was not significantly different (44 months vs not calculable). The incidence of adverse events (AEs) was similar between treatment groups (98% for BR vs 97% for R-chlorambucil), but the incidence of grade 3 AEs was higher for BR compared with R-chlorambucil (75% and 64%, respectively).…”

“…[6][7][8] In a multicenter phase II trial (CLL2M study), bendamustine/rituximab (BR) resulted in high ORR rates (88%; CR, 23%) in previously untreated patients (n=117; 26% were aged >70 years), with similar response and survival outcomes among the subgroup of elderly patients (aged >70 years). 6 After a median follow-up of 27 months, median PFS was 34 months and the OS rate was 90.5%.…”

“…8 In an interim analysis (126 evaluable patients; 58 treated with BR, 68 treated with R-chlorambucil; median age, 74 years; range, , at the median follow-up of 24 months, the ORR among the patients who received first-line therapy was 91% in the BR group (CR, NCCN Guidelines Insights For patients >65 y, the outcome was similar for both regimens with less toxicity for BR. BR may be a reasonable alternative for older patients otherwise eligible for chemoimmunotherapy and is associated with fewer myelosuppressive toxicities.…”

Rituximab in combination with chemotherapy for the treatment of chronic lymphocytic leukaemia in clinical practice

“…8 The recent phase III CLL10 trial, however, failed to show non-inferiority of R-B to R-FC as front-line therapy in fit patients, although less toxicity was observed with R-B, especially in patients > 65 years. 11 Treatments were comparable in other efficacy endpoints and overall safety. 10 In the phase IIIb MABLE trial, first-line treatment with R-B vs R-Clb increased complete remission rate (CRR) and median progression-free survival (PFS; 40 vs 30 months).…”

“…9 The addition of rituximab to frontline chlorambucil therapy (R-Clb) was suggested to improve efficacy with no unexpected adverse events (AEs) in a phase II study. 11 In the CLL11 study, the first large randomised phase III trial in patients with significant comorbidities, CRR was higher and PFS was longer with the combination of G-Clb than with R-Clb and single-agent Clb 12 and there was a significant overall survival (OS) benefit for both G-Clb and R-Clb arms compared with Clb alone. 11 Treatments were comparable in other efficacy endpoints and overall safety.…”