Efficacy of FLT3 Inhibitors in Patients with FLT3-Mutated Acute Myeloid Leukemia Unfit for Intensive Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: FLT3 inhibitors have demonstrated increased efficacy in patients with FLT3-mutated acute myeloid leukemia (AML). However, their effects on patients unfit for intensive chemotherapy remain undefined. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of FLT3 inhibitors in AML patients unfit for intensive chemotherapy. Methods: A systematic search was conducted between October 2024 and December 2024 across PubMed, Embase, and Cochrane Central. Studies included patients with AML who were unfit for intensive chemotherapy, treated with FLT3 inhibitors as monotherapy or in combination with low-intensity regimens, compared to standard low-intensity chemotherapy regimens. The primary outcome was the OS, defined as the proportion of patients alive at a specified time after treatment initiation or diagnosis. Statistical analysis was performed under a random effects model using Review Manager 8.11.0. Heterogeneity was assessed using I² statistics. Results: 745 patients from six randomized controlled trials (RCTs) were included. FLT3 inhibitors were used in 421 (56.51%) AML patients unfit for intensive chemotherapy. Among the six studies, one reported quizartinib combined with low-dose cytarabine, two reported gilteritinib monotherapy, one reported gilteritinib with azacitidine, one reported quizartinib monotherapy, and one reported decitabine with midostaurin. Follow-up ranged from 6.5 to 48 months. FLT3 inhibitors significantly improved OS (HR 0.52; 95% CI 0.35–0.78, P = 0.001; I² = 51%) compared to standard chemotherapy. However, the risk of grade ≥3 adverse events (RR 1.42; 95% CI 1.03–1.96, P = 0.03; I² = 0%) and QT interval prolongation (RR 3.49; 95% CI 1.43–8.51, P = 0.006; I² = 0%) was significantly higher in the FLT3 inhibitors group. Conclusion: FLT3 inhibitors, used either as monotherapy or in combination with low-intensity chemotherapy, improve OS in FLT3-mutated AML patients unfit for intensive chemotherapy. However, the increased risk of grade ≥3 adverse events and QT interval prolongation warrants careful monitoring in clinical practice.