The U.S. Food and Drug Administration (FDA) placed a partial hold on all ongoing clinical trials of venetoclax for the treatment of multiple myeloma (MM) due to an excessive amount of deaths in the phase III BELLINI study.
Venetoclax is already approved by the FDA to treat chronic lymphocytic leukemia and acute myeloid leukemia, and these findings do not impact the use of this drug in those patient populations.
Phase II trials of venetoclax in the MM population showed promising results, but the number of deaths involved in the larger BELLINI trial prompted the FDA’s hold. Although the trial met its primary endpoint of significantly improved progression-free survival (PFS), it also showed that patients who received venetoclax were at a two-fold higher risk for death compared with those who received placebo.
Patients already taking venetoclax for myeloma should follow the advice of their doctors who will make a case by case decision on benefits vs risks in terms of continuing therapy, & follow @US_FDA guidance. In partial hold, patients doing well on trial are permitted to continue
— Vincent Rajkumar (@VincentRK) March 23, 2019
The multicenter, randomized, double-blind BELLINI trial was assessing bortezomib and dexamethasone plus venetoclax or placebo in patients with relapsed/refractory MM who have received one to three prior lines of therapy and are sensitive or naïve to proteasome inhibitors. Patients in the venetoclax cohort had improve PFS (22.4 months vs. 11.5 months; hazard ratio [HR] = 0.63, 95% CI, 0.44-0.90), as well as significant improvements in the overall response rate (82% vs. 68%).
In a pre-planned analysis, 41 deaths (21.1%) were observed in the venetoclax cohort, 13 (6.7%) of which were treatment-related (HR=2.03; 95% CI, 1.042-3.945). Of these, eight were associated with an infection. Comparatively, 11 deaths (11.3%) were observed in the placebo group, one (1.0%) of which was treatment-related.
VERY INTRIGUING: FDA Puts Enrollment Hold on Venetoclax Myeloma Trials –> better ORR (82% vs 68%) and median PFS (2x: 22 vs 11 months) in venetoclax arm vs placebo, same rate AE's/SAE's, yet double number of deaths (22% vs 11%) with VEN!https://t.co/viqxVrVBks via @TargetedOnc
— Oscar Lahoud (@DrOscarLahoud) March 21, 2019