Hematology AdvisorASH Publishes New Guidelines for Newly Diagnosed AML

ASH 2025 guidelines update treatment recommendations for newly diagnosed AML in adults 55 and older, a population representing more than 75% of all AML diagnoses. Nine evidence-based recommendations address the full treatment arc, from initial therapy selection through postremission strategy, targeted agents, transplant eligibility, and end-of-life transfusion support.

Clinical Considerations

• Venetoclax-based combinations are now formally preferred over HMA or LDAC monotherapy for patients ineligible for conventional induction, with moderate-certainty evidence supporting mortality reduction and improved CR rates
• Guidelines retire the “intensive/nonintensive” distinction, recognizing venetoclax-based regimens as substantively active therapy requiring the same shared decision-making rigor as conventional 7+3
• For IDH1-mutated AML, azacitidine plus ivosidenib is preferred over monotherapy; for IDH2-mutated AML, HMA plus venetoclax is favored over enasidenib combinations
• FLT3 inhibitor addition to ALT is suggested for FLT3-mutated disease, primarily in conventional induction; benefit in HMA/LDAC plus venetoclax combinations remains unestablished
• Allo-HCT in first remission is conditionally suggested for nonfavorable-prognosis patients who are transplant-eligible, though evidence certainty is very low

Practice Applications

• Assess molecular profile at diagnosis, including IDH1, IDH2, and FLT3 mutation status, before finalizing treatment approach
• Consider patient age, functional status, and hospitalization preference when choosing between conventional induction and venetoclax-based regimens
• Continue HMA- or LDAC-based therapy indefinitely until progression or unacceptable toxicity rather than stopping after a fixed cycle count
• Evaluate allo-HCT candidacy in first remission for patients with nonfavorable cytogenetic or molecular risk who respond to initial ALT
• Review the full ASH EtD frameworks for TP53-mutated AML subgroups, where venetoclax benefit over monotherapy remains uncertain

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