ASH 2017 | Interim analysis of Phase III MURANO study shows improved outcomes with venetoclax plus rituximab in patients with CLL 

The 59th Annual Meeting & Exposition of the American Society of Hematology (ASH) took place in Atlanta, GA, on December 9–12, 2017. On Tuesday 12^th December, a late-breaking abstract session was held , with  abstract #LBA-2 being presented during this session titled “Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase 3 Murano Study” by John F Seymour Peter MacCallum Centre and Royal Melbourne Hospital, Melbourne, Australia, and colleagues.

 In a previous Phase Ib study, the combination of venetoclax and rituximab was found to be effective with acceptable safety results in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL). This data lead to evaluating this combination in a Phase III (MURANO) study to assess efficacy and safety compared with standard immunochemotherapy.

Study Highlights 

• 389 eligible patients with R/R CLL were included in the study
• Patients were randomized to receive either venetoclax with rituximab (VR) (n = 194) or bendamustine with rituximab (BR) (n = 195)
• Median follow-up = 23.8 months (0.0–37.4)
• Investigator-assessed (INV-assessed) progression-free survival (PFS) was superior for VR vs BR (HR = 0.17, 95%, CI 0.11–0.25, P < 0.0001)
• Median PFS VR vs BR:
  • not reached vs0 months
• INV-assessed overall response rate (ORR) for VR vs BR:
  • 3% vs 67.7% (Δ=25.6%, 95% CI, 17.9–33.3%)
• Minimal residual disease negativity (MRD–) was higher with VR vs BR:
  • 5% vs 23.1%; (Δ=60.4%, 95% CI, 52.3–68.6%)
• 2-year overall survival (OS) for VR vs BR:
  • 9% vs 86.6%; (HR = 0.48, 95% CI, 0.25–0.90, P = 0.0186)

 Safety

• Most frequent grade 3–4 adverse events (AEs) VR vs BR:
  • Neutropenia 57.7% vs 38.8%
  • Anemia 10.8% vs 13.8%
  • Thrombocytopenia 5.7% vs 10.1%

Dr Seymour concluded that VR was superior to BR in prolonging PFS and also that this trend was consistent across the subgroup analyses. He also noted that “the secondary endpoints were in favor of venetoclax and rituximab in particular the MRD negativity rate that was maintained over time. Thus overall, venetoclax plus rituximab should be considered as a suitable standard of therapy option for patients with relapsed or refractory CLL.”