Comparative Efficacy of Intensive Frontline Regimens in FLT3-Mutated AML: A Bayesian Network Meta-Analysis of Randomized Trials

FLT3-mutated acute myeloid leukemia (FLT3mut AML) is associated with poor outcomes. Although FLT3 inhibitors (FLT3is) combined with chemotherapy improve responses, long-term survival remains limited, and the optimal first-line strategy is unclear. We conducted a Bayesian network meta-analysis of eight randomized trials, including 1,793 patients, to compare intensive regimens for overall survival (OS). Treatments studied were 3 + 7 with midostaurin, quizartinib, sorafenib, gemtuzumab ozogamicin (GO), glasdegib, CPX-351, and decitabine. FLT3i-based regimens improved outcomes but showed attenuated effects in this analysis, consistent with prior data. The small population with FLT3 mutation treated with GO + 3 + 7 and CPX-351 provided good outcomes (SUCRA 86.1% and 71.7%), while glasdegib + 3 + 7 and decitabine resulted in less effective strategies. Notably, 3 + 7 + GO showed superior benefit despite limited FLT3mut subgroup evidence. Ongoing studies are exploring CPX-351, GO, and FLT3i combinations, as well as novel strategies. Prospective, mutation-specific trials are needed to define optimal therapy.