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BELLINI update: overall survival unfavourable for venetoclax overall

Researchers report that in the phase 3 BELLINI study, updated overall survival favored placebo over venetoclax (each with bortezomib and dexamethasone) in the overall population.

  • Shaji K Kumar, MD; Simon J Harrison, PhD; Michele Cavo, MD; Javier de la Rubia, MD; Rakesh Popat, FRCPath; Cristina Gasparetto, MD; et al.

  • June 25, 2025

  • The Lancet Haematology
  • The Lancet Haematology, Volume 12, Issue 8, Pages e574–e587
  • 10.1016/S2352-3026(25)00139-5

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Evidence before this study

At the time of the primary analysis publication, we did a PubMed search for clinical trial results published from Jan 1, 2011, to Dec 31, 2015, using the search terms “multiple myeloma,” “clinical trials,” “relapsed myeloma,” “refractory myeloma,” and “BCL-2 and myeloma.” There were no BCL-2 inhibitors available for the treatment of multiple myeloma when the BELLINI study was designed and initiated. Venetoclax, a highly selective, potent, oral BCL-2 inhibitor, has shown in vitro activity against myeloma cells and a synergistic effect when combined with bortezomib. The safety of venetoclax as a monotherapy, administered with dexamethasone, or combined with dexamethasone plus bortezomib was initially evaluated in two phase 1 studies, with findings of acceptable safety and promising preliminary efficacy. These results led to the randomised phase 3 BELLINI study of venetoclax or placebo combined with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. The BELLINI primary endpoint of progression-free survival was met in the primary analysis, but increased mortality in the venetoclax group led to additional subgroup analyses, revealing that venetoclax had better clinical outcomes in the t(11;14) and/or high BCL2 gene expression patient population.

Added value of this study

To our knowledge, BELLINI is the first randomised phase 3 clinical trial to evaluate the safety and efficacy of venetoclax combined with bortezomib and dexamethasone. In this analysis, the updated overall survival was unfavourable for the venetoclax group compared with the placebo group in the overall study population. In post-hoc analyses, the greatest survival improvements remained restricted to patients carrying biomarkers of t(11;14) and/or high BCL2 gene expression. Consistent with the primary analysis, the protocol-specified analyses of progression-free survival and response rates at the final overall survival analysis timepoint revealed that venetoclax added to bortezomib and dexamethasone significantly improved both outcomes in the overall study population.

Implications of all the available evidence

Results of BELLINI in patients with t(11;14) led to other clinical studies of venetoclax focusing on this biomarker subgroup and contributed to the inclusion of venetoclax as a clinical treatment option for patients with t(11;14)-positive multiple myeloma.

Source: The Lancet Haematology

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