The FLAG-IDA plus venetoclax regimen achieves very high MRD-negative remission rates. However, its similar efficacy in both frontline and first salvage settings suggests it might be more strategically deployed as a salvage therapy, avoiding its high toxicity in all patients upfront.

The modern practice of waiting for detailed diagnostic and genetic information before starting AML therapy provides a crucial, previously unavailable window of time for clinicians to conduct thorough fitness and geriatric assessments on their older patients.

To combat the significant myelosuppression from the standard 28-day venetoclax cycle in AML, many clinicians are adopting a strategy of performing a bone marrow biopsy around day 21 and pausing the drug if blast clearance is achieved to allow for hematologic recovery.

Initial studies combining menin inhibitors with venetoclax/azacitidine showed high remission rates but also high mortality. Using each agent at its full, 28-day dose caused severe, fatal myelosuppression, forcing protocol amendments to shorten drug exposure to manage toxicity.

While quizartinib's benefit is less pronounced in AML patients over 60, a specific genomic signature—the co-occurrence of FLT3-ITD, NPM1, and DNMT3A mutations—identifies a subset of older patients who derive a significant survival benefit, challenging age-based treatment decisions.

While Tumor Lysis Syndrome with venetoclax in newly diagnosed AML is rare, clinicians should be aware of a different, insidious complication: a potentially severe Cytokine Release Syndrome (CRS)-like reaction, particularly in patients with monocytic leukemia.

Traditional age cutoffs for AML therapy are becoming obsolete. A comprehensive fitness assessment, not just chronological age, should guide treatment, as some guidelines now classify patients as young as 55 as "older adults," a surprising shift for many clinicians.

The Spanish KIWI trial showed a surprising survival benefit for quizartinib in FLT3-ITD negative AML. The benefit was greatest in patients with NPM1 and DNMT3A mutations, suggesting the drug's efficacy extends beyond its primary target through other mechanisms.

A key advantage of the FLT3 inhibitor quizartinib over midostaurin is its demonstrated survival benefit in FLT3-ITD positive AML patients who do not proceed to an allogeneic transplant in their first remission. This makes it a more robust upfront option for a broader patient group.