Significantly higher PFS in R/R CLL with venetoclax-rituximab combo compared to bendamustine

An article published in the New England Journal of Medicine described a study evaluating the efficacy of the combination of venetoclax and rituximab in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL). The venetoclax-rituximab combination was compared to a combination of bendamustine and rituximab in patients randomly assigned to either treatment. The study was published on 22 March 2018, authored by John F Seymour, Director of the Haematology Department at the Peter MacCallum Cancer Centre, Victoria, Australia, and colleagues.

Study Overview

• Total number of patients involved in the open-label phase III study, N = 389, median age 65 years (22–85)
• Patients were randomized to receive either venetoclax and rituximab (n = 194) or bendamustine and rituximab (n = 195) that were included in the primary analysis
• 68 patients completed 2 years of treatment with venetoclax-rituximab and 154 patients completed the scheduled bendamustine-rituximab phase
• The primary endpoint was investigator-assessed (INV) progression-free survival (PFS)

Key Findings

Efficacy

• Median follow-up = 23.8 months
• Venetoclax-rituximab vs bendamustine-rituximab
  • Median PFS = not reached (NR) vs 17 months
  • 2-year INV-assessed PFS = 84.9% (95% CI, 79.1–90.6) vs 3% (95% CI, 28.5–44.0)
    • Hazard ratio (HR) = 0.17 (95% CI, 0.11–0.25)
  • 24-month overall survival (OS) rate = 91.9% vs 6%
    • HR = 0.48 (95% CI, 0.25–0.90)
    • Median OS for both groups were NR
  • Independent review committee-assessed overall response rate (ORR) = 92.3% vs 3%
  • INV-assessed ORR = 93.3% vs 7%
• 366 patients were tested for minimal residual disease (MRD) from peripheral-blood samples
  • Follow-up showed a higher rate of MRD clearance in venetoclax-rituximab (62.4%) than bendamustine-rituximab (13.3%) at 9 months and (83.5%) vs (23.1%), respectively, at any time during the trial

Safety

• Most common grade ≥3 adverse events venetoclax-rituximab vs bendamustine-rituximab
  • Neutropenia = 57.7% vs 8%
  • Infections = 17.5% vs 8%
  • Anemia = 10.8% vs 8%

The authors found that there was significantly higher PFS for R/R CLL patients with venetoclax-rituximab combination than with bendamustine-rituximab. They noted that the difference in response rates assessed by investigators and an independent review committee was due to differing interpretations of residual adenopathy on computed tomographic scans. No new safety signals emerged. The authors concluded that durability of responses would need to be determined to further assess the potential of venetoclax-rituximab therapy.