The mutational landscape predicts response and outcomes in elderly patients with acute myeloid leukemia treated with azacitidine or low dose cytarabine plus fludarabine

Treatment response and outcomes in older patients with newly diagnosed acute myeloid leukemia based on mutation status analysis by next generation sequencing using a custom 43 gene panel within the FLUGAZA phase III clinical trial, comparing azacitidine (n, 96) with fludarabine plus low-dose cytarabine (n, 111). Ninety-five percent of patients had at least one detectable mutation. Recurrent genetic abnormalities including FLT3, NPM1 and CEBPA mutations had no impact on overall survival in either treatment arm. Mutations in EZH2, U2AF1, DNMT3A, TET2 or ASXL1 were independent predictors of complete remission after the 3rd AZA cycle, and the presence of TET2 mutations and absence of TP53 mutations were associated with overall response to AZA after the 3rd cycle. Absence of mutations in NRAS or TP53 were independent predictive markers of complete remission after the 3rd FLUGA cycle. In the AZA-arm, cytogenetic risk was the only variable associated with early death, whereas in the FLUGA-arm white blood cell count, TP53 and NRAS mutations were associated with early death.