Multi-dimensional analysis of adult acute myeloid leukemia cross-continents reveals age-associated trends in mutational landscape and treatment outcomes (Acute Myeloid Leukemia Cooperative Group & Alliance for Clinical Trials in Oncology).

The outcome of patients with acute myeloid leukemia (AML) worsens with increasing age. Dichotomization into "younger" and "older" patients is clinically routine and often dictates treatment options. We aimed to delineate whether molecular genetic features and/or outcome measures support assorting patient populations by age, including division into "younger" and "older" groups. We analyzed 2823 adult AML patients enrolled onto frontline chemotherapy-based clinical protocols of two cooperative study groups from USA and Germany who were profiled molecularly via targeted sequencing platforms. Frequencies of gene mutations and cytogenetic findings were depicted in 5-year age increments. Clinical outcomes of 2756 AML patients were analyzed with respect to molecular features, genetic-risk groups and age. Age-associated distributions of gene mutations and cytogenetic abnormalities were similar in both cohorts. There was almost linear shortening of overall survival with increasing age among all patients (P < 0.001) and within 2022 European LeukemiaNet-defined genetic-risk groups, with survival decreasing as age increased (favorable-risk, P < 0.001; intermediate-risk, P < 0.001; adverse-risk, P < 0.001). Although mutational profiles and outcomes of the youngest patients differed from those of older patients, there was no age cut-off identifying "younger" and "older" patients. These findings support more age-associated flexibility for drug approval and trial eligibility.