SOHO State of the Art Updates and Next Questions Acute Myeloid Leukemia: Current Status and Next Questions

Advances in understanding leukemogenesis in acute myeloid leukemia (AML) have led to new drug approvals in the past 4 years. Ongoing preclinical research is expected to produce more targeted therapies, reducing the need for traditional chemotherapy, while also enhancing classification systems and patient prognostication. In newly diagnosed AML, the mainstay of induction still is 7+3 regimen. In unfit adults, combination of venetoclax and hypomethylating agent has emerged to be the standard of care. Introduction of FLT3 inhibitors with the 7 plus 3 regimen has improved outcomes in FLT3 mutant patients. IDH inhibitors have recently been approved for induction in medically unfit adult. Studies focusing on triplet regimen are underway. FLT3 inhibitors and IDH inhibitors have also been approved for Relapsed and Refractory AML. Menin inhibitors are another novel class of drugs which are currently being studied for both de novo as well as relapsed and refractory AML. For consolidation in fit patients, high dose cytarabine and Allogenic transplant are still the mainstay of treatment whenever feasible. FLT3 inhibitors have been studied as long term maintenance after allogenic stem cell transplantation. As potent regimens achieve high-quality remissions, the need for sensitive assays to detect measurable residual disease (MRD) and predict relapse risk will grow. MRD monitoring using flow cytometry and molecular methods have been effective with cytarabine-based treatments and will be crucial for venetoclax therapies. Eradicating MRD is a key goal for AML subsets, with research focused on targeted and immune- based therapies to eliminate MRD and understand relapse through clonal evolution. Allogeneic stem cell transplant is the most effective treatment for residual leukemia in resistant AML but is limited by toxicity and donor availability. Immune-based strategies, including antibodies and bispecific molecules, show promise in early trials, and safer cellular therapies could expand treatment options.