The Prognostic Impact of Additional Molecular and Cytogenetic Abnormalities on AML Patients with NPM1- and/or FLT3-ITD Mutations Receiving Intensive Chemotherapy: Real-World Data from the Greek Registry

Background/Objective: The prognostic impact of additional cytogenetic aberrations and molecular abnormalities (such as MDS-related mutations, mutations in myeloid genes and the KRAS/NRAS mutations) in patients with NPM1- and/or FLT3-ITD-mutated AML remains elusive. Methods: This retrospective, multicentre study of real-world data aimed to investigate the impact of these mutations and cytogenetic abnormalities on the prognosis of patients with NPM1- and/or FLT3-ITD-mutated AML, treated with intensive chemotherapy. Results: In a cohort of 161 patients, the only parameters identified to affect the outcomes (EFS and OS) were the age of the patient, primary refractory disease, the presence of a NPM1 mutation and the use of allogenic stem cell transplantation (allo-SCT) within the first complete remission. More specifically, ages below the median conferred significantly improved outcomes, whereas primary refractory disease exhibited a negative correlation with the EFS and OS. Subsequent subgroup analysis, stratifying patients into three groups (Group 1: NPM1^mutated/FLT3^wt; Group 2: NPM1^mutated/FLT3^mutated; Group 3: NPM1^wt/FLT3^mutated). revealed that allo-SCT in CR1 improved the outcomes (EFS and OS) in Groups 2 and 3, but had no additional impact in Group 1. Conclusions: Age, primary refractory disease and allogenic stem cell transplantation in the first complete response were found to have a prognostic impact on outcomes, Interestingly, no significant association was detected between the poor prognostic cytogenetic abnormalities or the presence of additional mutations in myeloid genes, MDS-related genes or KRAS/NRAS genes and the outcomes in any group of patients.