Management of Acute Myeloid Leukemia: A Review - PubMed
5 hours ago
- #AML
- #targeted therapy
- #hematologic malignancy
- Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with historically poor outcomes, especially in older adults and high-risk molecular cases.
- Advances in genomic profiling have led to targeted therapies beyond conventional treatments like cytarabine-anthracycline induction and hypomethylating agents.
- Key evolving therapeutic areas include menin inhibition, FLT3 inhibition, IDH inhibition, and treatments for TP53-mutated AML.
- Menin inhibitors (e.g., revumenib, ziftomenib) show significant activity in NPM1-mutated and KMT2A-rearranged AML, with ongoing studies on combination strategies to combat resistance.
- FLT3 inhibitors (e.g., midostaurin, gilteritinib, quizartinib) improve survival in FLT3-mutated AML and may benefit selected FLT3-wild-type cases based on gene expression signatures.
- IDH inhibitors (e.g., ivosidenib, enasidenib) are effective in IDH-mutated AML, though questions remain about their efficacy compared to venetoclax.
- TP53-mutated AML remains challenging, with short-lived responses to hypomethylating-agent/venetoclax regimens and poor overall survival; early-phase therapies show preclinical promise but lack clinical efficacy.
- Targeted therapies have improved outcomes in molecularly defined AML subsets, but TP53-mutated AML still has a dismal prognosis, highlighting the need for better treatments.
- Future research should focus on biomarker-driven approaches, novel drug combinations, and mechanistic insights to refine AML treatment and improve survival across subsets.