Gilteritinib maintenance therapy after allogeneic hematopoietic stem cell transplantation in FLT3-mutated AML: A systematic review and meta-analysis

Abstract Background FMS-like tyrosine kinase 3(FLT3) mutations confer a high relapse risk in acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Gilteritinib, a selective FLT3 inhibitor, is approved for FLT3-mutant AML, both as first line and in relapsed/ refractory cases, but its role as maintenance post-HSCT remains under investigation in clinical trials. Methods We conducted a systematic review and meta-analysis to evaluate the efficacy of Gilteritinib as maintenance therapy following allo-HSCT in patients with FLT3-mutated AML. PubMed, Embase, and Cochrane databases were searched from January 2017 to July 2025 for randomized and observational studies reporting overall survival (OS) and relapse-free survival (RFS) outcomes. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a fixed-effects model. Heterogeneity was assessed using the I² statistic. Results A total of 552 patients were included from three observational studies and two randomized controlled trials. Pooled risk ratios were estimated using a Mantel–Haenszel random-effects model to account for clinical variability and differences in study populations. Gilteritinib maintenance was associated with a statistically significant improvement in RFS (RR 1.32; 95% CI: 1.07–1.62; I² = 34%; p = 0.010) compared to arms without maintenance. For OS, four studies with a total of 490 patients showed a non-significant trend favoring Gilteritinib (RR 1.15; 95% CI: 0.95–1.40; I² = 38%; p = 0.16). The largest contribution came from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1506 (MORPHO) trial by Levis in 2024 (48% weight for RFS, 54.4% for OS), which included a sample size of 356 participants. A subgroup analysis of the trial showed that patients who showed such a survival benefit had measurable residual disease pre- or post-HSCT. Given the small number of studies, publication bias could not be formally assessed. The most common adverse effects observed across studies were hematological toxicities, acute and chronic graft versus host disease (GVHD), transaminase and creatine phosphokinase elevations, and drug rash. But despite these side effects, an analysis of the health-related quality of life (HRQOL) between the two groups in the MORPHO trial showed no significant differences between the groups Conclusion Gilteritinib maintenance therapy post-allo-HSCT is associated with significantly improved relapse-free survival in FLT3-mutated AML. These findings support its consideration as a post-transplant maintenance strategy, especially in patients with peri-HSCT MRD positivity. While the data is promising, most included studies are retrospective. Due to a lack of uniform reporting across studies, a pooled analysis of the toxicity profile, especially of GVHD incidence, could not be performed. However, some individual studies reported a higher incidence of GVHD in the Gilteritinib arm, raising the possibility of an association that warrants further investigation and larger randomized controlled trials.