Dr. Steensma on the Utility of Venetoclax in MDS

David P. Steensma, MD, associate professor of medicine, Harvard Medical School, clinical director, Center for Prevention of Progression, Edward P. Evans Chair in Myelodysplastic Syndromes Research, and institute physician, Dana-Farber Cancer Institute, discusses the potential utility of venetoclax (Venclexta) in myelodysplastic syndrome (MDS).

While venetoclax is not approved in MDS, it has off-label usage, explains Steensma. Venetoclax in combination with hypomethylating agents may elicit more durable responses for patients with high-risk, p53-mutant MDS who do not achieve deep remissions with hypomethylating agents alone.

At the 2019 ASH Annual Meeting, two phase Ib studies (NCT02942290; NCT02966782) evaluating the safety and efficacy of venetoclax in combination with azacitidine (Vidaza) in patients with MDS were presented.

Among 57 evaluable treatment-naïve patients with high-risk disease, 18 experienced an objective response with the combination of venetoclax plus azacitidine. Additionally, 11 patients had stable disease.

Among 24 evaluable patients with relapsed/refractory disease in the second trial, 12 experienced an objective response with the combination. Additionally, 31% of patients experienced stable disease with the combination versus 75% with venetoclax alone.

Both studies reported treatment-related deaths resulting from infections. More patients appeared to tolerate the combination as upfront therapy after the dosing schedule was revised and prophylactic antibiotics were implemented, concludes Steensma.