Venetoclax Improves Outcomes vs Bendamustine in Chronic Lymphocytic Leukemia
Researchers randomly assigned 389 patients with R/R CLL to VR or BR study arms. Patients were stratified by del(17p) status, responsiveness to previous therapy, and geographic region.
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Compared with bendamustine plus rituximab (BR), venetoclax plus rituximab (VR) significantly prolongs progression-free survival (PFS) among patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL), according to a late-breaking abstract presented at the 2017 American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia.1
Previous studies demonstrated that venetoclax is highly effective in CLL, leading to improved overall response (ORR), complete response (CR), and minimal residual disease negativity (MRD-) rates, but head-to-head comparisons with standard chemoimmunotherapy regimens were previously unperformed.
For the open-label phase 3 MURANO study (ClinicalTrials.gov Identifier: NCT02005471), researchers randomly assigned 389 patients with R/R CLL to VR or BR study arms. Patients were stratified by del(17p) status, responsiveness to previous therapy, and geographic region. MRD was assessed at screening, months 4 and 9, and during 3-monthly follow-up visits.
After a median follow-up of 23.8 months, investigator-assessed median PFS was superior in the VR arm, with PFS not reached for patients receiving VR compared with 17.0 months among patients in the BR arm (hazard ratio [HR], 0.17; 95% CI, 0.11-0.25; P < .0001); this PFS benefit was observed in all evaluated subgroups.
Twenty-four-month PFS estimates were 84.9% in the VR arm and 36.3% in the BR arm. An Independent Review Committee confirmed a comparable PFS benefit for VR (HR, 0.19; 95% CI, 0.13-0.28; P < .0001).
Patients treated with VR also had improvements in overall survival (OS; HR, 0.48; 95% CI, 0.25-0.90), investigator-assessed ORR (VR: 93.3% vs BR 67.7%; 95% CI, 17.9-33.3%), and CR/CR with incomplete bone marrow recovery (26.8% and 8.2% in VR and BR, respectively).
Patients in the VR arm had more durable MRD- rates, at 83.5% compared with 23.1% in the BR arm (95% CI, 52.3%-68.6%).
Grade 3 to 4 neutropenia occurred at a higher frequency among patients in the VR arm, but there was no increase in the rate of febrile neutropenia or grade 3 to 4 infection. Approximately 5% and 6% of patients in the VR and BR arms died because of AEs, respectively.
The authors concluded that “enhanced disease control was achieved in a multinational setting with an acceptable safety profile, without significant [tumor lysis syndrome], demonstrating that treatment with VR resulted in outcomes superior to that of BR for [patients] with R/R CLL.”
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- Seymour JF, Kipps TJ, Eichhorst BF, et al. Venetoclax plus rituximab is superior to bendamustine plus rituximab in patients with relapsed/refractory chronic lymphocytic leukemia – results from pre-planned interim analysis of the randomized phase 3 MURANO study. Oral presentation at: American Society of Hematology 59th Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA.