# Safety profile of FLT3 inhibitors in acute myeloid leukemia: a systematic review and meta-analysis of adverse events

## TL;DR

This study compares the safety of FLT3 inhibitors used in treating acute myeloid leukemia and finds they are generally as safe as standard treatments.

## Contribution

A systematic review and meta-analysis comparing the safety profiles of first and second-generation FLT3 inhibitors in AML.

## Key findings

- FLT3 inhibitors are not associated with a significant increase in adverse events compared to standard treatments.
- No meaningful differences in AE risk were observed among midostaurin, gilteritinib, and quizartinib.
- Gilteritinib showed a higher risk of elevated ALT compared to other FLT3 inhibitors.

## Abstract

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Approximately 30% of patients present alterations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene, which are associated with poor prognosis. FLT3 inhibitors – midostaurin (first-generation), gilteritinib and quizartinib (second-generation) – have been developed to block FLT3 activation. Given the need of optimizing treatment in FLT3-mutated AML, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the safety profiles of FLT3 inhibitors. Following the PRISMA statement, we searched Embase, MEDLINE and Cochrane Library. The Cochrane Risk of Bias Tool for RCTs was used for quality assessment. Of 2132 references, seven RCTs, involving 2409 adult patients, met inclusion criteria: quizartinib and midostaurin in two trials each and gilteritinib in three. The most frequently reported adverse events (AEs) were classified under the System Organ Class (SOC) Blood and lymphatic system disorders (N = 5474, 58.4% of them related to FLT3 inhibitors). The most frequently observed non-hematological AEs were gastrointestinal disorders, pyrexia, elevated ALT/AST and headache. FLT3 inhibitors are not associated with a significant increase in the risk of AEs compared to standard treatments. No meaningful differences in AE risk were observed among the three drugs. The only exception was an higher risk of ALT increased with gilteritinib (RR = 2.40, 95% CI: 1.16–4.95). Future studies should stratify safety outcomes by demographic and clinical characteristics and incorporate long-term follow-up for a more comprehensive safety assessment in clinical practice.

The online version contains supplementary material available at 10.1007/s10238-026-02093-8.