Prognostic impact of ASXL1 mutations in ND AML treated with Ven-based LIT

Results from a single-center retrospective study, evaluating the prognostic impact of ASXL1 mutations in adults with newly diagnosed (ND) acute myeloid leukemia (AML) treated with venetoclax (Ven)-based lower-intensity therapy (LIT), were published in Cancer by Marvin-Peek et al. The analysis included 554 adults treated with LIT + Ven (ASXL1-mutated [ASXL1^m], n = 73; ASXL1 wild-type [ASXL1^wt], n = 481), including 239 patients classified as favorable risk per European LeukemiaNet (ELN) 2024 classification. Outcomes were assessed by ASXL1 status and treatment backbone.

Key data: Among ELN 2024 favorable-risk patients, ASXL1^m vs ASXL1^wt was associated with lower composite complete remission (CRc) rates (69% vs 90%; p < 0.001), shorter median overall survival (OS; 16.2 vs 35.4 months; p = 0.003), and numerically shorter median relapse-free survival (RFS; 14.9 vs 26.2 months; p = 0.09), resembling ELN 2024 intermediate-risk disease. On multivariable analysis, ASXL1^m remained independently associated with inferior OS (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.06–2.55; p = 0.03), with similar inverse probability-weighted results (HR, 1.70; 95% CI, 1.13–2.57; p = 0.01). The impact was most pronounced with cladribine (Clad) + low-dose cytarabine (LDAC) + Ven (n = 95), where the CRc rate was 58% in patients with ASXL1^m AML vs 93% in those with ASXL1^wt AML (p = 0.02), and median OS was 17 months vs not reached, respectively (p = 0.024). Meanwhile, among patients receiving hypomethylating agent (HMA) + Ven-based therapy, ASXL1^m vs ASXL1^wt AML showed a nonsignificant trend toward lower CRc rates and shorter median OS.

Key learning: ELN 2024 favorable-risk ASXL1^m AML treated with Ven-based LIT may be more appropriately classified as intermediate-risk, supporting integration of ASXL1 status and treatment backbone choice into first-line risk assessment and treatment planning.