Cytogenetics and gene mutations influence survival in older patients with acute myeloid leukemia treated with azacitidine or conventional care

Cancer research · Lymphoma · TP53

Azacitidine improves overall survival compared with conventional care in older patients with acute myeloid leukemia, particularly among those with adverse‑risk cytogenetics and specific chromosome 5, 7, and 17 abnormalities.

Older patients with newly diagnosed acute myeloid leukemia (AML) in the phase 3 AZA-AML-001 study were evaluated at entry for cytogenetic abnormalities, and a subgroup of patients was assessed for gene mutations. Patients received azacitidine 75 mg/m^2/day x7 days (n = 240) or conventional care regimens (CCR; n = 245): intensive chemotherapy, low‑dose cytarabine, or best supportive care only. Overall survival (OS) was assessed for patients with common (occurring in ≤10% of patients) cytogenetic abnormalities and karyotypes, and for patients with recurring gene mutations. There was a significant OS improvement with azacitidine vs CCR for patients with European LeukemiaNet‑defined Adverse karyotype (HR 0.71 [95%CI 0.51–0.99]; P = 0.046). Azacitidine‑treated patients with –5/5q‑, –7/7q‑, or 17p abnormalities, or with monosomal or complex karyotypes, had a 31–46% reduced risk of death vs CCR. The most frequent gene mutations were DNMT3A (27%), TET2 (25%), IDH2 (23% [R140, 15%; R172, 8%]), and TP53 (21%). Compared with wild‑type, OS was significantly reduced among CCR‑treated patients with TP53 or NRAS mutations and azacitidine‑treated patients with FLT3 or TET2 mutations. Azacitidine may be a preferred treatment for older patients with AML with Adverse‑risk cytogenetics, particularly those with chromosome 5, 7, and/or 17 abnormalities and complex or monosomal karyotypes. The influence of gene mutations in azacitidine‑treated patients warrants further study.

This study demonstrates that azacitidine confers a survival advantage over conventional care in older AML patients with high‑risk cytogenetics, supporting its preferential use in this subgroup and highlighting the prognostic significance of specific genetic alterations for treatment selection.

Evidence level: Irányelv / elfogadott gyakorlat. Magas szintű klinikai elfogadottság.

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