The U.S. Food and Drug Administration (FDA) has issued a warning to health-care professionals and clinical investigators about the risks associated with the investigational use of venetoclax in patients with multiple myeloma (MM), following a review of clinical trials data that showed an increased risk of death among venetoclax-treated patients.
The FDA reviewed interim results from the phase III BELLINI trial, which is evaluating the efficacy of venetoclax in combination with bortezomib and dexamethasone in patients with previously treated MM, compared with placebo. According to a safety and efficacy analysis conducted on November 26, 2018 (the prespecified data cutoff date), there were 41 deaths among the 194 patients in the venetoclax-containing arm (21.1%), compared with 11 deaths among the 97 patients in the placebo arm (11.3%), translating to a two-fold higher risk of death with venetoclax (hazard ratio = 2.03; 95% CI 1.04-3.94; p value not reported).
Based on these findings, the FDA suspended enrollment in BELLINI and other ongoing clinical trials of venetoclax in MM. Currently enrolled patients who are receiving clinical benefit with venetoclax are permitted to continue treatment in these trials after they reconsent. This action does not apply to patients taking venetoclax for an approved indication, including acute myeloid leukemia and chronic lymphocytic leukemia or small lymphocytic lymphoma.
The FDA said it is working with AbbVie, the trial’s sponsor, to determine the extent of the safety issue. The agency also encouraged health-care professionals and patients to report any adverse events related to the use of venetoclax to the agency’s MedWatch Adverse Event Reporting program.
Source: FDA announcement, March 21, 2019.