Impact of FLT3 inhibitors on the outcomes of FLT3-ITD mutated acute myeloid leukemia following allogeneic hematopoietic stem cell transplant: A systematic review and meta-analysis

BACKGROUND: Acute Myeloid Leukemia (AML) with FLT3-ITD mutations is associated with high post-transplant relapse rates. FLT3 inhibitor (FLT3i) maintenance therapy following allogeneic hematopoietic stem cell transplantation (allo-HCT) has emerged as a promising strategy to improve outcomes in this high-risk population. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating FLT3i maintenance therapy versus standard of care (SOC) after allo-HCT in patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A comprehensive search of PubMed, Embase, CENTRAL, and ClinicalTrials.gov was performed in accordance with PRISMA guidelines. Primary outcomes included relapse-free survival (RFS), overall survival (OS), and FLT3i-related adverse events. Pooled hazard ratios (HRs) and relative risks (RRs) were calculated using the "meta" package in R (version 4.4.0). RESULTS: Four RCTs including 701 patients (ages 18-78) met inclusion criteria. FLT3i maintenance significantly reduced relapse (HR 0.50; 95 % CI: 0.34-0.74) and mortality (HR 0.63; 95 % CI: 0.44-0.91) compared to SOC. Hematologic toxicity (RR 2.12; 95 % CI: 1.67-2.70) and chronic GVHD (RR 1.18; 95 % CI: 1.00-1.41) were more frequent in the FLT3i group. Rates of acute GVHD (RR 1.05; 95 % CI: 0.78-1.41) and hepatotoxicity (RR 1.09; 95 % CI: 0.72-1.66) were comparable. Interestingly, skin toxicity was lower with FLT3i (RR 0.36; 95 % CI: 0.16-0.84). CONCLUSION: FLT3i maintenance significantly improves RFS and OS in FLT3-ITD-mutated AML post-allo-HCT, though at the cost of increased hematologic toxicity and chronic GVHD. Further studies are needed to define optimal agents, duration, and patient selection to balance efficacy with tolerability.