SOHO State of the Art Updates and Next Questions: The Past, Present and Future of Venetoclax-Based Therapies in AML.

The use of venetoclax in combination with hypomethylating agents (HMA) has changed the paradigm for the treatment of acute myeloid leukemia (AML) in elderly patients and those unfit for intensive chemotherapy. A phase 3 study has shown superior response rates and improved overall survival for patients treated with venetoclax + azacitidine compared with the previous standard of care, azacitidine alone. This success has led to multiple exciting follow-up studies, including investigations related to the discovery of predictors of response, relapse, and the mechanism of action of this therapy. While venetoclax + HMA has shown significant benefit in elderly patients unfit for chemotherapy, further questions remain as to how this therapy can be expanded into other populations including relapsed or refractory patients and younger newly diagnosed patients with adverse risk features. In this article, we discuss the clinical outcomes of AML with venetoclax + HMA, established and potential predictors of response to this regimen, its mechanisms of action, and speculate on the future of venetoclax + HMA therapy in AML.