Kater AP, et al. - Researchers performed this study to report minimal residual disease (MRD) kinetics and updated outcomes (with all patients off treatment) of the MURANO study which reported significant progression-free survival (PFS) benefit for fixed-duration venetoclax-rituximab vs bendamustine-rituximab in relapsed/refractory chronic lymphocytic leukemia. Compared with bendamustine-rituximab, a continued benefit was observed for venetoclax-rituximab, with all patients having finished treatment. A longer PFS was predicted by undetectable MRD (uMRD) rates, which were found to be durable. This establishes the influence of peripheral blood (PB) MRD on the benefit of fixed-duration, venetoclax-containing treatment. After completion of 2 years of venetoclax-rituximab, low conversion to detectable MRD and sustained PFS were seen, this implied that this regimen was feasible.

Methods

• Two years of venetoclax plus rituximab during the first six cycles, or six cycles of bendamustine-rituximab were randomly administered to study participants.
• Focus was laid on PFS (primary end point) and on secondary end points that included safety and peripheral blood (PB) MRD status—at cycle 4, 2 to 3 months after end of combination therapy (EOCT), and every 3 to 6 months thereafter.

Results

• This study included a total of 194 patients.
• Of these, 174 (90%) and 130 (67%) completed the venetoclax-rituximab phase and 2 years of venetoclax, respectively.
• Superiority with regard to PFS and overall survival was noted during a median follow-up of 36 months, in comparison to bendamustine-rituximab (hazard ratio, 0.16 [95% CI, 0.12 to 0.23]; and hazard ratio, 0.50 [95% CI, 0.30 to 0.85], respectively).
• Venetoclax-rituximab resulted in a higher rate of PB undetectable MRD (uMRD; less than 10^-4) at EOCT (62% v 13%) with superiority sustained through month 24 (end of therapy).
• Overall, longer PFS was predicted by uMRD status at EOCT.
• Among those with detectable MRD, improved PFS was predicted by low-level MRD (10^-4 to less than 10^-2) vs high-level MRD (10^-2 or greater).
• Disease progression (11 high-level MRD, three low-level MRD) was seen only in 12% (16 of 130) of patients at a median of 9.9 months (range, 1.4 to 22.5 months) after completing fixed-duration venetoclax-rituximab.
• Findings revealed that 70% and 98% of patients with uMRD remained in uMRD and without disease progression, respectively, at the end of therapy.