Researchers continue to focus on novel combination approaches in the treatment of chronic lymphocytic leukemia (CLL). In the phase 3 MURANO study, the efficacy and safety of venetoclax in combination with rituximab (VenR) in relapsed/refractory (R/R) CLL was evaluated as fixed-duration treatment compared with standard bendamustine + rituximab (BR). An initial analysis established a superior progression-free survival (PFS) of VenR over BR at median follow-up of 23.8 months (Seymour JF, et al. N Engl J Med. 2018). Here, researchers present longer-term outcome data with a median follow-up of 36 months.
Patients were randomized to receive 6 cycles of VenR followed by venetoclax 400 mg once daily for a maximum of 2 years, or 6 cycles of BR. In total, 389 patients were enrolled in the VenR (n = 194) and BR (n = 195) arms. In the VenR arm, 174 (90%) completed the VenR combination phase and 130 (67%) had completed 2 years of venetoclax treatment. For BR, 154 (79%) had completed 6 cycles.
With a median time of 9.9 months off venetoclax after 2 years of treatment, PFS with VenR remained superior to BR. Three-year PFS estimates were 71.4% for VenR versus 15.2% for BR, and 3-year overall survival estimates were 87.9% versus 79.5%, respectively. The treatment effect with VenR was consistent across subgroups, including age, number of prior regimens, and mutational status.
In terms of safety, the VenR regimen was well-tolerated, with no new safety signals. Notable grade 3/4 adverse events in the VenR arm (≥10%) included neutropenia (58.8%) and anemia (10.8%).
Researchers concluded that this study demonstrates clinically meaningful benefit of the VenR regimen in all patients with R/R CLL, with no new safety signals present.
Seymour JF, et al. ASH 2018. Abstract 184.