Prognostic impact of co-mutations in adults with -mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by the accumulation of cytogenetic and molecular abnormalities. Isocitrate dehydrogenase 1 and 2 () mutations occur in 11% to 20% of adults with AML. The outcome of -mutated AML is heterogeneous and affected by co-mutational patterns. We retrospectively analyzed 118 patients with -mutated AML who were retrieved from 1597 patients newly diagnosed with AML and treated with intensive chemotherapy. Univariate analysis revealed the mutation was a favorable factor ( = 0.019) for overall survival (OS), whereas the mutation was consistently associated with a poor outcome (3-year OS, 52.0%; 3-year relapse-free survival [RFS], 44.8%; and 3-year cumulative incidence of relapse [CIR], 42.6%). Interestingly, the mutation still identified patients with a poorer prognosis, even when measurable residual disease (MRD) was negative after 2 courses of chemotherapy. In a multivariate regression model, age, mutation and MRD positivity were retained as independent adverse markers for OS, RFS, and CIR. In the absence of the or -ITD mutations, the mutation identified patients with a very favorable OS (3-year OS, 96.3% and 86.3%, respectively). Finally, hematopoietic stem cell transplantation in first complete remission significantly improved RFS ( = 0.015) and there was a trend toward improvement in OS ( = 0.282) for patients with the mutation but it did not benefit 2 subgroups with the +/+/- and +/+/-ITD- genotypes. In summary, this study provides a reference for risk stratification and treatment implications for patients with -mutated AML as well as for comparison with results of IDH inhibitor- or venetoclax-based combination therapy.