Dr. Davies on Promise of Venetoclax in Relapsed/Refractory Myeloma

Faith E. Davies, MD, professor in the Department of Medicine and director of the Clinical Myeloma Program at NYU Langone Health’s Perlmutter Cancer Center, discusses the use of venetoclax (Venclexta) as a precision medicine approach in patients with relapsed/refractory multiple myeloma.

Several precision medicine approaches are currently being evaluated in multiple myeloma, says Davies. In multiple myeloma, different groups have been targeted for years. For example, younger, less fit patients with the disease have received transplants, and patients with t(4;14) have received bortezomib or another proteasome inhibitor, says Davies.

Now, there is a shift toward using other drugs, such as venetoclax (Venclexta), for patients who have an t(11;14). Originally, venetoclax was used in patients with chronic lymphocytic leukemia; it is known to be an anti—BCL-2 drug, says Davies. It appears that patients who have a t(11;14) have high BCL-2 levels, and many of those patients respond exceptionally well to venetoclax.

However, safety data from the phase III BELLINI trial suggested a possible increase in toxicity with the agent, which led to the FDA’s decision to suspend trials examining the drug in multiple myeloma, explains Davies. Results from the trial showed a higher rate of patient deaths with venetoclax combined with bortezomib (Velcade) and dexamethasone versus placebo in patients with relapsed/refractory myeloma.

Specifically, the rate of deaths was 21.1% in the venetoclax arm versus 11.3% in the placebo arm. Moreover, 6.7% of the deaths were determined to be treatment emergent in the venetoclax arm versus just 1.0% in the placebo arm.

The partial hold has since been lifted, and the investigation of the drug is moving forward in this patient population. The results thus far with this approach appear to be very promising, concludes Davies.