Beat AML: Prognostic impact of IDH mutations in older patients with ND AML

Results from a retrospective analysis of the Beat AML trial (NCT03013998), evaluating the prevalence and prognostic impact of IDH mutations in older adults (aged ≥60 years) with newly diagnosed (ND) acute myeloid leukemia (AML) (N = 1,023), were published in Haematologica by Hoff et al. In the outcome-evaluable cohort (n = 1,002), patients received intensive chemotherapy (IC), lower-intensity therapy (LIT), or supportive care/unknown regimens; most patients treated with LIT received hypomethylating agent (HMA)-based treatment.

Key data: IDH mutations were detected in 28% of patients, including IDH1 mutations in 9.7%, IDH2 mutations in 18.9%, and mutations in both IDH1 and IDH2 in 1.0%. Among patients treated with IC (n = 187), IDH mutation was not prognostic for overall survival (OS; p = 0.76). Among patients receiving LIT (n = 705), IDH mutation was associated with longer median OS compared with wild-type IDH (IDH^wt; 15.6 vs 10.2 months; hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.51–0.78; p < 0.001), primarily driven by IDH2 mutation (HR, 0.56; 95% CI, 0.44–0.72). Among patients who received an HMA-based LIT regimen (n = 666), median OS was 16.7 vs 10.2 months for IDH mutation vs IDH^wt (HR, 0.62; 95% CI, 0.49–0.77; p < 0.001), driven by IDH2 mutation vs IDH^wt (18.5 vs 10.2 months; HR, 0.55; 95% CI, 0.43–0.72; p < 0.001). IDH2 mutation remained prognostic after excluding patients receiving an IDH inhibitor (HR, 0.60; 95% CI, 0.41–0.89), while IDH mutation was not prognostic with HMA + venetoclax (p = 0.42).

Key learning: IDH2 mutations confer a favorable prognosis in older adults with ND AML receiving HMA-based LIT, supporting continued evaluation of targeted therapy combinations with LIT regimens in IDH-mutated AML.