DNMT3A Co-Mutation and Real-World Clinical Outcomes With Gilteritinib in FLT3-Mutated Acute Myeloid Leukaemia Across Molecular Subgroups.

INTRODUCTION: Molecular co-mutations modulate outcomes in FLT3-mutated AML treated with gilteritinib; real-world data stratified by DNMT3A co-mutation status are lacking. METHODS: We retrospectively analysed 29 adults with R/R FLT3-mutated AML treated at two Italian centres. Sixteen patients with complete molecular profiling were stratified into three subgroups by DNMT3A and NPM1 co-mutation status. RESULTS: Overall response rate was 89.7% (26/29). DNMT3A-mutated subgroups showed prolonged OS from gilteritinib initiation versus wild-type group (median not reached vs. 8.8 months; 12-month OS 78% vs. 17%). CONCLUSIONS: These hypothesis-generating data suggest that DNMT3A co-mutation status is associated with differential gilteritinib outcomes, supporting comprehensive molecular profiling in FLT3-mutated AML. TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.