Venetoclax Plus Bortezomib and Dexamethasone Combination Therapy Demonstrates Inferior Overall Survival for Patients With R/R MM

Among patients with relapsed/refractory (R/R) multiple myeloma (MM), venetoclax combined with bortezomib and dexamethasone treatment demonstrated inferior overall survival (OS) outcomes and superior progression-free survival (PFS) compared with placebo according to results from the multicenter, phase 3 BELLINI clinical trial published in The Lancet Haematology. 

Previous research has found venetoclax plus bortezomib and dexamethasone demonstrated superior progression-free survival compared with placebo for patients with R/R MM. Researchers conducted a randomized, double-blind phase 3 trial to determine the survival outcomes and safety profile of venetoclax plus bortezomib and dexamethasone among patients who previously received 1 to 3 prior lines of therapy. 

Patients were randomized 2 to 1 to receive venetoclax (800 mg orally) once daily or placebo with bortezomib (1.3 mg/m2 subcutaneously or intravenously) and dexamethasone (20 mg orally) for 8 cycles (21 days). The primary end point was PFS and safety.

Overall, 291 patients were randomized to receive venetoclax (n = 194) or placebo (n = 97). At a median follow-up of 45.6 (interquartile range [IQR], 43.6 to 48.3) months, the median PFS for patients treated with venetoclax was 23.4 (95% confidence interval [CI], 16.2 to 26.4) months, which was higher than patients treated with placebo (11.4 months; 95% CI, 9.5 5o 14.6; hazard ratio [HR], .58; 95% CI, 0.43 to 0.78; P = .00026). The median overall survival (OS) was not reached for either the venetoclax group (95% CI, 44.4 to not estimable) or the placebo group (95% CI 44.0 to not estimable). 

In terms of safety, rates of grade 3 or 4 adverse thrombocytopenia were higher in the placebo group than the venetoclax group (40% vs 26%), while rates of grade 3 or 4 neutropenia were higher in the venetoclax group than the placebo group (30% vs 8%). Of the 193 patients treated with venetoclax, 4 patients had treatment-related adverse events which led to death, including 2 patients with pneumonia. 

“Final overall survival analysis in the BELLINI study showed overall survival favoring placebo over venetoclax and progression-free survival favoring venetoclax over placebo, indicating venetoclax usage should be avoided in the general relapsed or refractory multiple myeloma population,” the researchers concluded.

Source:

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. The Lancet Haematology. Published online June 27, 2025. doi:10.1016/s2352-3026(25)00139-5