Outcomes of patients with R/R FLT3mut+ AML treated with maintenance gilteritinib therapy after hematopoietic stem cell transplantation

Patients with acute myeloid leukemia (AML) with FMS -like tyrosine kinase 3 ( FLT3 ) mutations have a poor prognosis, even after hematopoietic stem cell transplantation (HSCT). Targeted maintenance therapy with gilteritinib is now recommended post-HSCT in de novo measurable residual disease-positive FLT3 mut+ AML patients. However, the benefits of post-HSCT gilteritinib maintenance in relapsed and refractory (R/R) disease are less clear. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to collate and describe the body of evidence (from inception of databases to April 29, 2024) assessing the clinical outcomes of gilteritinib post-HSCT therapy in patients with R/R FLT3 mut+ AML. Eight studies (2 randomized controlled; 6 observational) reporting clinical outcomes in a total of 134 adult patients with FLT3 mut+ AML were included in the narrative synthesis. Six were single-arm studies, and 2 included a comparator group without maintenance therapy after transplantation. From time of HSCT, 1- and 2-year overall survival (OS) rates ranged from 72.3%-100% (n=55) and 55.8%-60.0% (n=41), respectively, and 1- and 2-year relapse-free survival (RFS) rates were 46.7%-100.0% (n=27) and 46.7%-80.0% (n=13), respectively. Comparative data suggest that gilteritinib as post-HSCT maintenance therapy may improve clinical outcomes of patients with R/R FLT3 mut+ AML versus no gilteritinib maintenance. However, no definite conclusions can be drawn from the limited clinical data available in this setting. Further well-designed studies with uniformity in defining OS and RFS are required to provide further insight into this strategy for the high-risk R/R FLT3 mut+ AML population. • The benefits of post-HSCT gilteritinib maintenance in R/R FLT3 mut+ AML are unclear • This SLR described clinical outcomes of post-HSCT gilteritinib in R/R FLT3 mut+ AML • From HSCT, 1- and 2-year OS rates were 72.3%-100% and 55.8%-60.0%, respectively • From HSCT, 1- and 2-year RFS rates were 46.7%-100.0% and 46.7%-80.0%, respectively • Clinical data were limited; further well-designed studies are required