Beat AML trial: Impact of IDH mutations in older patients with ND AML treated with HMA-based therapy

Results from a retrospective analysis examining the incidence and prognostic impact of isocitrate dehydrogenase (IDH) mutations (IDH^m) in 1,023 older patients (≥60 years) with newly diagnosed (ND) acute myeloid leukemia (AML) were published by Hoff et al. in Haematologica. Eligible patients were enrolled in the phase Ib/II Beat AML trial (NCT03013998). IDH^m were detected in 28% of patients, including IDH1^m (9.7%), IDH2^m (18.9%), and IDH1^m + IDH2^m (1.0%). The outcome analysis included 1,002 patients, of whom 705 received lower-intensity therapy; among these, 666 were treated with hypomethylating agent (HMA). The outcome analyzed was overall survival (OS).

Key data: The most commonly co-occurring mutations with IDH^m were DNMT3A, NPM1, and SRSF2 (p < 0.001 each). Among patients treated with HMA, the median OS was prolonged in patients with IDH2^m compared with wild-type IDH (IDH^wt) (18.5 vs 10.2 months; p < 0.001). IDH1 was not predictive of survival outcomes, while IDH2 remained prognostic of OS after excluding patients who received IDH inhibitors (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41–0.89). Favorable outcomes were observed when IDH co-mutated with a TP53 (p = 0.043) or myelodysplasia-related gene mutation (p = 0.006).

Key learning: IDH2 mutations demonstrate favorable prognosis in older patients with ND AML treated with HMA-based therapy, supporting further investigation of targeted therapy combinations with lower-intensity regimens in this population.