Venetoclax plus bortezomib and dexamethasone significantly improved survival compared with bortezomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma (MM), according to a study published in The Lancet Oncology.
However, increased mortality was seen in the venetoclax group due to infections, which the authors said highlights “the importance of appropriate selection of patients for this treatment option.”
The randomized, double-blind, multicenter, phase III BELLINI trial included adult patients with relapsed or refractory MM from 90 hospitals in 16 countries. Eligible patients had an Eastern Cooperative Oncology Group performance status score of ≤2 and received one to three prior therapies.
Between July 19, 2016, and October 31, 2017, 291 patients were randomized 2:1 to receive venetoclax 800 mg per day orally (n=194) or placebo (n=97) plus bortezomib 1.3 mg/m2 subcutaneously or intravenously and dexamethasone 20 mg orally.
After a median follow-up of 18.7 months (range, 16.6-21.0 months), median progression-free survival according to independent review committee (primary endpoint) was 22.4 months with venetoclax (95% confidence interval [CI], 15.3 to not estimable) versus 11.5 months with placebo (95% CI, 9.6-15.0; hazard ratio, 0.63; 95% CI, 0.44-0.90; P=0.010).
The most common grade ≥3 treatment-related adverse events (AEs) that occurred in the venetoclax and placebo cohorts were neutropenia (n=35 [18%] vs. n=7 [7%]), pneumonia (n=30 [16%] vs. n=9 [9%]), thrombocytopenia (n=28 [15%] versus n=29 [30%]), anemia (n=28 [15%] vs. n=14 [15%]), and diarrhea (n=28 [15%] vs. n=11 [11%]). Serious treatment-related AEs occurred in 93 patients (48%) in the venetoclax group and 48 (50%) in the placebo group.
Eight (4%) treatment-related fatal infections occurred in the venetoclax group, while none were reported in the placebo group. Three deaths in the venetoclax group (two from pneumonia and one from septic shock) were considered treatment-related, while no deaths in the placebo group were deemed treatment-related.