By: Kerri Fitzgerald
Final results of the phase 3 BELLINI trial showed no improvement in overall survival (OS) for patients with multiple myeloma (MM) when venetoclax was added to bortezomib and dexamethasone treatment.
Venetoclax “should be avoided in the general relapsed or refractory MM population,” according to Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues, who published the findings in The Lancet Haematology.
The randomized, double-blind, multicenter trial previously showed improved progression-free survival (PFS) with the venetoclax combination, though there was a trend toward early mortality.
Between July 19, 2016, and October 31, 2017, 291 patients were randomized 2:1 to receive daily oral venetoclax 800 mg (n=194) or placebo (n=97) plus bortezomib 1.3 mg/m2 subcutaneously or intravenously and dexamethasone 20 mg orally.
Most patients were male (52%) and White (65%). Patients received one to three prior therapies.
After a median follow-up of 45.6 months, median OS was not reached in the venetoclax and placebo groups (hazard ratio [HR], 1.19; P=0.39). Median PFS was 23.4 months with venetoclax versus 11.4 months with placebo (HR, 0.58; P=0.00026).
While the OS was “unfavorable” for the venetoclax cohort in this study, the researchers did observe a survival benefit with the venetoclax combination in patients with t(11;14) mutation and/or high BCL2 gene expression.
The most common grade 3/4 adverse events in both groups were thrombocytopenia (51 [26%] with venetoclax versus 38 [40%] with placebo) and neutropenia (58 [30%] versus 8 [8%], respectively).
Four treatment-related adverse events resulted in death in the venetoclax group compared with none in the placebo cohort.
The study was funded by AbbVie and Genentech.
Reference
Kumar SK, Harrison SJ, Cavo M, et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed or refractory multiple myeloma (BELLINI): final overall survival results from a randomised, phase 3 study. Lancet Haematol. 2025;12(8):e574-e587. doi:10.1016/S2352-3025(25)00139-5
