Acute myeloid leukemia (AML) has entered an era of molecular stratification. FLT3 and IDH1/IDH2 mutations occur in approximately 30–40% of cases, representing the most prevalent actionable targets guiding targeted therapy selection alongside or instead of intensive chemotherapy.
A BCL-2 inhibitor combined with a hypomethylating agent demonstrated superior overall survival versus hypomethylating agent alone in intensive chemotherapy-ineligible newly diagnosed AML (VIALE-A), establishing a new standard of care. Selective IDH1 and IDH2 inhibitors have demonstrated single-agent activity in relapsed/refractory disease; IDH1 inhibitor plus azacitidine showed superior event-free and overall survival in newly diagnosed IDH1-mutant AML. Emerging triplet combinations generate encouraging signals but heighten differentiation syndrome risk, requiring vigilant monitoring. Measurable residual disease (MRD) assessment is increasingly integrated into response evaluation and allogeneic transplant decision-making.
Hematologists and oncologists managing newly diagnosed or relapsed/refractory AML, particularly IDH1/2, FLT3, or NPM1-mutant disease, will benefit from discussion of targeted therapy combinations, MRD monitoring, and transplant eligibility considerations.
How has the availability of BCL-2 and IDH-targeted therapies changed your induction and consolidation decision-making for newly diagnosed AML patients eligible for intensive chemotherapy? What role does MRD assessment play in your AML management, including transplant timing and post-remission therapy, and what methodology do you find most clinically actionable?
MRD is increasingly central to decision-making, particularly after induction/consolidation and before transplant. I find multiparameter flow cytometry and molecular MRD testing when a trackable mutation is available most actionable, as persistent MRD can support earlier transplant or intensified post-remission strategies, whereas deep MRD negativity may help refine the need and timing for transplant.