SOHO State of the Art Updates and Next Questions | The Evolving AML Treatment Paradigm

The treatment paradigm for fit, younger adults with acute myeloid leukemia (AML) is evolving toward the frontline use of lower-intensity, better-tolerated therapies that more effectively target disease biology. For over 45 years, intensive chemotherapy (IC) has endured as the cornerstone of induction therapy for fit AML patients. Clinical outcomes have slowly improved during this time; however, long-term survival remains suboptimal, and IC-related toxicity is significant. For older AML patients, clinical outcomes have been transformed by the introduction of hypomethylating agents in combination with venetoclax (HMA-Ven) because of its potent anti-leukemic activity and improved tolerability. The success of HMA-Ven highlights the importance of rationally designed therapies that exploit leukemia dependencies while minimizing systemic toxicity. We outline the development of IC and HMA-Ven while also describing the first studies to directly compare these distinct modalities in younger patients. We explore growing evidence that guides the use of lower-intensity therapy in younger AML patients who would traditionally receive IC but may achieve favorable outcomes using HMA-Ven. When considering the use of HMA-Ven in younger patients, we highlight several important issues including the need for improved patient selection for HMA-Ven, optimal implementation of HMA-Ven in patients planned for allogeneic stem cell transplant (HCT), evaluation of post-HCT outcomes following induction using HMA-Ven, utilization of measurable residual disease (MRD) during treatment with HMA-Ven, and the prospect of triple combinations incorporating novel targeted agents.