Four-Year Analysis of Murano Study Confirms Sustained Benefit of Time-Limited Venetoclax-Rituximab (VenR) in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)

Introduction: Venetoclax (Ven) is a highly selective oral inhibitor of key apoptosis regulator BCL-2, which is overexpressed in CLL. MURANO (a randomized Phase III study) compared fixed-duration VenR with standard bendamustine-rituximab (BR) in R/R CLL. The superior progression-free survival (PFS) of VenR versus BR was established in the first pre-planned analysis (Seymour et al. N Engl J Med 2018); continued PFS benefit was seen with longer follow-up and after all patients (pts) had completed therapy (Kater et al. J Clin Oncol 2019). We now present data from a further analysis (median follow-up 48 months) when all pts had been off Ven treatment for median 22 months. Methods: As previously published, pts were randomized to 6 cycles of VenR then Ven 400mg once daily for 2 years in total, or 6 cycles of BR. PFS status was based on investigator assessment. Central analysis of minimal residual disease (MRD) status in peripheral blood (PB) was performed at Cycle 4, end of combination treatment (EOCT) then every 3-6 months. Pts were categorized as undetectable MRD (uMRD;