Dr. Cowan on the Role of Venetoclax in Multiple Myeloma

Andrew J. Cowan, MD, an assistant professor of medicine at University of Washington and hematologist/oncologist at Seattle Cancer Care Alliance, discusses the role of venetoclax (Venclexta) in multiple myeloma.

The oral BCL-2 inhibitor has shown a lot of promise in the treatment of patients with multiple myeloma. Data from the 2017 ASH Annual Meeting showed a 40% overall response rate (ORR) for patients who harbored t(11;14) by fluorescence in situ hybridization. This led to further studies such as the phase III BELLINI trial, in which patients with relapsed multiple myeloma were randomized to receive venetoclax with bortezomib/dexamethasone or bortezomib/dexamethasone alone. Notably, t(11;14) did not serve as an exclusion criteria in the trial. In early 2019, the study was halted due to an increased risk of death observed in patients who received venetoclax.

Despite these safety concerns, venetoclax has the potential to play an important role for patients with relapsed multiple myeloma, especially in those with t(11;14), says Cowan. Given the fact that these patients did not have a substantial increase of death, the use of venetoclax in myeloma may be contingent on a biomarker-driven approach with t(11;14).

Cowan has treated several patients with venetoclax. Most recently, a patient with t(11;14) and plasma cell leukemia who hadn't responded to anything, responded well to venetoclax. Moving forward, it will be important to understand the cause of the increased toxicity in the overall population receiving venetoclax before it can be definitively said that venetoclax doesn't have a role in myeloma.