Venetoclax with bortezomib and dexamethasone improves response rates for patients with relapsed or refractory multiple myeloma, particularly in patients with a specific genetic profile, according to research published in The Lancet Oncology.

Many patients with multiple myeloma experience long-term remission, but relapse rates remain high. The randomized, phase 3, double-blind BELLINI trial ( Identifier: NCT02755597) compared venetoclax, an oral BCL-2 inhibitor, combined with bortezomib and dexamethasone to placebo with bortezomib and dexamethasone. In the study, 291 patients were randomly assigned 2:1 to each group with 194 in the venetoclax group and 97 in the placebo group.

The venetoclax group had a median progression-free survival (PFS) of 22.4 months compared with 11.5 months in the placebo group. A larger proportion of patients in the venetoclax group achieved a complete response or better with minimal residual disease negativity compared with those in the placebo group. Median overall survival (OS) was not reached in either treatment group.

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Both treatment groups experienced adverse events, and the venetoclax group had a higher rate of mortality; 99% of patients in each group experienced treatment-related adverse events, and approximately half of patients in each group (48% in the venetoclax group vs 50% in the placebo group) experienced serious treatment-emergent events. More fatal infections occurred in the venetoclax group, and 13 treatment-emergent deaths were reported in the venetoclax group compared with 1 in the placebo group.

Multiple myeloma has a range of disease characteristics, with clinical features driven by underlying genetic abnormalities. The authors noted that previous research has found patients with BCL-2 dependent disease respond better to venetoclax. BCL-2 dependency differs between patients and is affected by the expression and presence of BCL-2 protein family abnormalities; one such abnormality is t(11;14) translocation.

In a subset of 35 patients with t(11;14) translocation, median PFS was not reached in the venetoclax group, compared to 9.5 months in the placebo group. Patients with high BCL2 expression (66 in venetoclax and 32 in placebo) had a PFS of 22.4 months with venetoclax compared with 9.9 months with placebo.

In the trial, approximately 26% of patients in the venetoclax group had a complete response or better. However, venetoclax has a higher risk of death and should be considered in biologically selected patients who have t(11;14) translocation and high BCL2 expression. The limitations of this study include a small sample size and small subset of patients with t(11;14) translocation.

“The finding that patients with t(11;14) and those with high BCL2 expression appear to have a more [favorable] risk-benefit profile than patients without t(11;14) and with low BCL2 expression suggests that a biomarker-driven approach might be appropriate for the use of venetoclax in multiple myeloma,” the authors wrote.

“This concept is being explored in an ongoing phase 3 trial ( Identifier: NCT03539744) that is comparing venetoclax and dexamethasone or pomalidomide and dexamethasone in patients with t(11;14)-positive relapsed or refractory multiple myeloma,” concluded the investigators.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Kumar SK, Harrison SJ, Cavo M, et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. Published online October 29, 2020. doi:10.1016/S1470-2045(20)30525-8

This article originally appeared on Hematology Advisor