EHA24 Congress: Venetoclax Combination Therapy in Resistant Myeloma
Posted: Monday, June 17, 2019
Based on the findings of the phase III BELLINI trial of nearly 300 patients with relapsed or resistant multiple myeloma, the addition of the BCL2 inhibitor venetoclax to bortezomib/dexamethasone improved outcomes versus bortezomib/dexamethasone and placebo. However, the triplet therapy was associated with an increased risk of death in an unfavorable benefit-risk profile in a broad population. Shaji Kumar, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues presented their data at the 24th European Hematology Association (EHA24) Congress in Amsterdam (Abstract LB2601).
“In t(11;14) patients, in addition to improvements in progression-free survival, a positive trend in overall survival with venetoclax was observed, suggesting that a biomarker-driven approach with venetoclax may be most appropriate in multiple myeloma,” the investigators concluded.
At data cutoff, 194 had received venetoclax plus bortezomib/dexamethasone and 97, placebo plus bortezomib/dexamethasone. All study patients had had between one and three prior therapies and were considered to be either sensitive or naive to proteasome inhibitors. And 18% had high-risk cytogenetics.
With a median follow-up of 18.7 months, the median progression-free survival was 22.4 months with venetoclax vs 11.5 months with placebo (hazard ratio = 0.630; P = .01). The duration of response was not reached with venetoclax and was 12.8 months with placebo; the median overall survival was not reached in either arm, but the investigators reported that it favored placebo.
The subgroup analyses revealed that the median progression-free survival had not been reached with the triplet therapy in patients with t(11;14) or in those with high BCL2 expression. Moreover, high BCL2 expression, high-risk cytogenetics, or International Staging System III disease (b2-M level > 5.5 mg/L) were found to be linked to decreased survival outcomes in those treated with venetoclax.
In terms of toxicity, 51 deaths—40 in the venetoclax arm and 11 in the placebo arm—were reported. The most common treatment-related adverse events in both treatment arms were diarrhea, nausea, constipation, and fatigue.
Disclosure: The study authors’ disclosure information may be found at ehaweb.org.
