SOHO State of the Art Updates and Next Questions: Is Favorable-risk AML Always Favorable?

The 2022 European LeukaemiaNet acute myeloid leukemia (AML) classification allocates AML with t(8;21) RUNX1::RUNX1T1 fusion and AML with inv(16) or t(16;16) CBFB::MYH11 fusion (collectively, core-binding factor AML), AML with NPM1 without FLT3-ITD mutation and AML with CEBPA bZIP in-frame mutation into the favorable-risk strata based on initial molecular diagnostics. Generally, these entities have a relatively low risk of relapse (< 30%-40%) and many patients (> 50%-60%) survive long-term with intensive chemotherapy alone. However, there is growing literature that patterns of co-mutation, and more importantly, postremission measurable residual disease (MRD) status, modify these risks dynamically; necessitating an adaptive approach to optimize patient outcomes. In this review, we summarize evidence on how molecular and MRD features could assist clinicians in identifying high-risk patients within these favorable-risk subgroups, and where escalation of therapy, including with allogeneic transplantation in first remission, may be beneficial.