Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival
Post-Treatment Follow-Up of the MURANO Phase III Study
PURPOSE The MURANO study demonstrated significant progression-free survival (PFS) benefit for fixedduration venetoclax-rituximab compared with bendamustine-rituximab in relapsed/refractory chronic lymphocytic leukemia. With all patients off treatment, we report minimal residual disease (MRD) kinetics and
METHODS Patients were randomly assigned to 2 years of venetoclax plus rituximab during the first six cycles, or six cycles of bendamustine-rituximab. Primary end point was PFS. 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—were secondary end points.
RESULTS Of 194 patients, 174 (90%) completed the venetoclax-rituximab phase and 130 (67%) completed 2 years of venetoclax. With a median follow-up of 36 months, PFS and overall survival remain superior 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). Patients who received venetoclax-rituximab achieved a higher rate of PB undetectable MRD (uMRD; less than 1024 ) at EOCT (62% v 13%) with superiority sustained through month 24 (end of therapy). Overall, uMRD status at EOCT predicted longer PFS. Among those with detectable MRD, low-level MRD (1024 to less than 1022 ) predicted improved PFS compared with high-level MRD (1022 or greater). At a median of 9.9 months (range, 1.4 to 22.5 months) after completing fixed-duration venetoclax-rituximab, overall only 12% (16 of 130) of patients developed disease progression (11 high-level MRD, three low-level MRD). At the end of therapy, 70% and 98% of patients with uMRD remained in uMRD and without disease progression, respectively.
CONCLUSION With all patients having finished treatment, continued benefit was observed for venetoclaxrituximab compared with bendamustine-rituximab. uMRD rates were durable and predicted longer PFS, which establishes the impact of PB MRD on the benefit of fixed-duration, venetoclax-containing treatment. Low conversion to detectable MRD and sustained PFS after completion of 2 years of venetoclax-rituximab demonstrate the feasibility of this regimen.
|Persistent URL||dx.doi.org/10.1200/jco.18.01580, hdl.handle.net/1765/115195|
|Journal||Journal of Clinical Oncology|
Kater, A.P, Seymour, J.F, Hillmen, P, Eichhorst, B, Langerak, A.W, Owen, C.J, … Kipps, T.J. (2018). Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival. Journal of Clinical Oncology, 37(4), 269–26+. doi:10.1200/jco.18.01580