FLT3 Inhibitors As Maintenance Therapy Post Allogenic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients with FLT3 Mutations; A Systematic Review and Meta-Analysis

Approximately 20-30% of adult patients with acute myeloid leukemia (AML) have an FMS-like tyrosine kinase 3 (FLT3) mutation, which falls in the intermediate risk category for relapse and overall survival per ELN 2022 classification, and eligible patients undergo allogeneic hematopoietic cell transplantation (allo-HCT). FLT3 inhibitors (FLT3i) are used in induction and relapsed settings, but recent studies suggest that FLT3i may reduce the risk of post-transplant relapse. We performed this systematic review and meta-analysis to evaluate the efficacy of FLT3i as post-transplant maintenance therapy in AML patients.

A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Clinicaltrials.gov from inception to March 29, 2024. Studies were included that evaluated response [overall survival (OS), relapse-free survival (RFS), and leukemia-free survival (LFS)], in comparisons between FLT3i and control groups. RevMan version 5.4.1 was used for statistical analysis. A random effect model with inverse variance as the statistical method was used for hazard ratio (HR) and 95% confidence interval (CI).

Of 1698 included studies, the data consists of 13 observational studies, comprising 4402 patients (52% males and 48% females), who met the inclusion criteria. Of the sample size, 36% of patients received FLT3i therapy, while the control group comprised 63.9% of patients. Patient age ranged from 14 to 78 years (median 49 years in intervention). AML subtypes included de novo (29%), secondary to antecedent hematological disorder (AHD) (1.7%), secondary to therapy (0.8%), and unspecified (68.5%). The follow-up period extended from 5.7 to 47.7 months. Nine out of thirteen studies reported cytogenetic risk. The type of FLT3i regimen used was reported as 54% Sorafenib followed by 15% Midostaurin, and only 8% Gilteritinib and Quizartinib. FLTi as maintenance in post-transplant patients significantly improved OS [ HR; 0.56] 95% CI [0.46-0.68], P< 0.00001, I² 31%], RFS [HR 0.56; 95% CI (0.50-0.64), P< 0.00001, I² 0%] and LFS [HR 0.47; 95% CI (0.38-0.57), P< 0.00001, I² 0%] as compared to control.

This meta-analysis demonstrates the efficacy of FLT3i as a post-transplant maintenance therapy for preventing relapse in AML patients.

No relevant conflicts of interest to declare.