Venetoclax Plus Rituximab Induces Sustained Survival in Relapsed/Refractory CLL

A longer-term follow-up of the MURANO study demonstrated sustained progression-free survival (PFS) and overall survival (OS) benefits with venetoclax plus rituximab versus bendamustine plus rituximab in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). The results were presented at the 2019 ASH Annual Meeting.

In a follow-up analysis from the randomized, phase III study, 389 patients with relapsed/refractory CLL were randomized to receive six cycles of venetoclax plus rituximab (n=194) or bendamustine plus rituximab (n=195).

At data cutoff (May 8, 2019), all patients were off treatment after a median follow-up of 48 months. After a median follow-up of 22 months (range, 1-35 months) since venetoclax completion, the PFS benefit of venetoclax plus rituximab was sustained compared with bendamustine plus rituximab (hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.14-0.25; P<0.0001).

Four-year PFS estimates were 57.3% (95% CI, 49.4-65.3) with venetoclax plus rituximab versus 4.6% (95% CI, 0.1-9.2) with bendamustine plus rituximab. Among patients who completed two years of venetoclax therapy (n=130), 18- and 24-month post-treatment cessation PFS estimates were 75.5% (95% CI, 67.4-83.7) and 68.0% (95% CI, 57.6-78.4), respectively. Thirty-five patients in this cohort experienced disease progression.

Sustained OS benefit was also demonstrated with venetoclax plus rituximab versus bendamustine plus rituximab (HR, 0.41; 95% CI, 0.26-0.65; P<0.0001), and four-year OS rates were 85.3% and 66.8%, respectively.

Patients who attained peripheral blood undetectable minimal residual disease (MRD) had particularly durable responses, and among patients treated with venetoclax plus rituximab who had detectable MRD, low MRD was associated with improved PFS compared with high MRD.

Researchers reported no new serious adverse events associated with the treatment regimens. Three second primary malignancies occurred, excluding non-melanoma skin malignancies, in one patient in the bendamustine plus rituximab group and two patients in the venetoclax plus rituximab group. 


Seymour JF, Kipps TJ, Eichhorst BF, et al. Four-year analysis of Murano study confirms sustained benefit of time-limited venetoclax-rituximab (VenR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Abstract 355. Presented at the 2019 ASH Annual Meeting, December 8, 2019; Orlando, Florida.