KRAS Mutations Predict Inferior Post-Remission Outcomes in Newly Diagnosed Acute Myeloid Leukemia With MAPK Pathway Mutations.

Somatic mutations in the MAPK signaling pathway are frequently identified at AML diagnosis; however, their impact on treatment resistance and long-term survival remains unclear. We conducted a retrospective study of patients with newly diagnosed MAPK-mutated AML seen at the University of Iowa Health Care. The endpoints were overall survival (OS), composite complete remission (CRc) following induction therapy, and relapse-free survival (RFS). Logistic and Cox regression models were used. Seventy-four patients were included and 62 were induction eligible. Of the 62 patients receiving treatment, intensive induction was administered in 52.7%. The estimated 5-year OS was 28.9%. On multivariable analysis, European LeukemiaNet 2022 adverse risk (hazard ratio [HR]: 3.56, 95% confident interval [CI]: 1.52-8.32) and KRAS mutation (HR: 2.14, 95% CI: 1.10-4.17) conferred inferior OS. Abnormal karyotype (odds ratio [OR]: 0.25, 95% CI: 0.07-0.89) and increasing age (OR: 0.97, 95% CI: 0.94-0.99) were associated with decreased odds of achieving a CRc. The median RFS after achieving a CRc was 13.3 months. We found that KRAS mutation conferred an inferior effect on OS and RFS but not CRc. These findings suggest that KRAS mutations may confer adverse prognostic significance and warrant validation in larger, multicenter cohorts.