Abstract
Objectives To compare the outcomes of FLT3-ITD mutated AML patients who underwent allo-HSCT in first complete remission (CR1) with those who remained on continuous chemotherapy plus a FLT3-targeted inhibitor as consolidation therapy.
Methods Consecutive patients newly diagnosed with FLT3-ITD mutated AML and treated at Peking University Institute of Hematology between January 2018 and January 2025 were enrolled; last follow-up was 1 July 2025. Induction therapy comprised chemotherapy plus a FLT3-targeted inhibitor or azacitidine plus venetoclax. MRD relapse was defined as conversion from MRD negativity to positivity detected by multiparameter flow cytometry. Events were hematologic relapse, MRD relapse, or death from any cause. Event-free survival (EFS) was measured from diagnosis to the first event or last follow-up; relapse-free survival (RFS) was calculated from the date of CR/CRi to hematologic relapse or last follow-up/death from other causes; overall survival was calculated from diagnosis to death or last follow-up. Kaplan–Meier estimates were compared by log-rank test. Propensity-score matching (PSM) adjusted for baseline covariates; uni- and multivariable Cox regression identified covariates associated with EFS, RFS, and overall survival.
Results Data on 303 consecutive newly diagnosed AML patients with FLT3-ITD mutation classified as ELN intermediate-risk cohort were collected. 150 subjects receiving chemotherapy plus sorafenib or venetoclax plus azacitidine as induction therapy, achieving CR/CRi and received 1 or 2 cycles of consolidation were included in this study. The median age was 46 years (range, 16-74 years). With a median follow-up of 30 months (range, 6-83 months) in surviving patients, 80 patients chose to remain on chemotherapy plus FLT3 inhibitor and 70 received allo-HSCT. In multivariate analysis allo-HSCT was associated with favorable EFS (p = 0.02) and RFS (p = 0.001). 102 patients were included in the PSM analysis, 51 patients chose to remain on chemotherapy plus FLT3 inhibitor and 51 received allo-HSCT. There were no difference in EFS (p = 0.005), RFS (p = 0.002) and survival (p = 0.41) between the 2 cohorts. In 120 CR1 subjects with negative MRD after 1-2 cycle of consolidation, 66 chose to remain on chemotherapy plus FLT3 inhibitor and 54 received allo-HSCT. In PSM analysis, 41 patients chose to remain on chemotherapy plus FLT3 inhibitor and 41 received allo-HSCT. 2 cohorts had comparable EFS (p = 0.15), RFS (p = 0.17) and survival (p = 0.63). However, in the 30 CR1 subjects with positive MRD after 1-2 cycle of consolidation, 14 chose to remain on chemotherapy plus FLT3 inhibitor and 16 received allo-HSCT. Allo-HSCT cohort had significant advantage in EFS (p < 0.001) and RFS (p < 0.001), but did not show significant difference in survival (p = 0.12).
ConclusionIn the era of FLT3-targeting inhibition therapy, FLT3-ITD mutated AML patients who achieve MRD negativity after 1-2 cycles receiving chemotherapy plus FLT3 inhibitor exhibit comparable outcomes to those undergoing allo-HSCT in CR1; however, those with positive MRD still can benefit from allo-HSCT. These findings require validation through larger prospective studies to establish definitive treatment guidelines.
