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

Genetic Abnormalities in Multiple Myeloma: Prognostic and Therapeutic Implications

“…Recently, a phase 3 trial testing the addition of venetoclax to bortezomib and dexamethasone showed significantly increased response rates (ORR 85% vs. 70%) and PFS (not reached vs. 9.9 months, p < 0.0001) without increasing mortality in patients with high BCL2 levels or t (11;14). However, the mortality in the experimental arm was higher in patients without t (11;14) due to increased infection rate [20,21]. According to these data, two phase 2 trials with venetoclax in combination with carfilzomib, and with daratumumab plus bortezomib, are now recruiting, and a phase 3 trial involving a combination with pomalidomide and dexamethasone is progress.…”

Paving the way to precision medicine in multiple myeloma

“…Based upon results from the M12-901 study, the phase 3 BELLINI trial randomized patients 2:1 to venetoclax or placebo in combination with bortezomib and dexamethasone [16]. Of 291 patients, 194 were randomized to the venetoclax arm and 97 to the placebo.…”

“…In a posthoc analysis, high BCL2 expression also identified a patient population that derived a PFS benefit without increased mortality with venetoclax. The median progression-free survival in patients with high BCL2 gene expression (n = 98) was 22.4 months (95% CI 22.4-not estimable) with venetoclax and 9.9 months (9.0-14.0) with placebo (HR 0.24 [95% CI 0.12-0.48]; p < 0 • 0001) [16]. This was noticeably contrasted by poorer outcomes in the low BCL2 and non-t(11;14) group which had lower overall survival rates compared with placebo (n = 130, HR = 3.13, 95% CI = 1.2-8.13, p = 0.019) [16].…”

Prognostic and Predictive Factors in Newly Diagnosed Multiple Myeloma Patients with Early Mortality with Prediction Matrix and Three and Five-Year Overall Survival

“…T (11;14) is observed in 16-24% of MM patients and has specifically gained interest with the use of the novel agent venetoclax, a BCL2 inhibitor. Currently, the use of venetoclax was stopped due to an early signal for increased death in early clinical trials due to a higher rate of infections [54]. A large, US, multicenter prospective observational cohort study did not demonstrate any impact of t (11;14) on PFS, or OS [55].…”