Use of FLT3 inhibitors in acute myeloid leukemia remission induction or salvage therapy: systematic review and meta-analysis

Background: Previous studies showed that FLT3 inhibitors played an important role in acute myeloid leukemia (AML) therapy. However, discrepancies remain regarding the association between FLT3 inhibitors use and prognosis of AML patients in clinical trials. Aim: The aim of this study was to evaluate the effect of FLT3 inhibitors on the treatment of AML in a systematic review and meta-analysis. Materials and methods: PubMed, Embase, and Cochrane Library databases were searched for studies published before August 2017 that used FLT3 inhibitors in AML. Fixed-and random-effect models were used, and between-study heterogeneity was assessed. Results: A total of 26 studies fitting our inclusion and exclusion criteria were included. The FLT3 status of patients and main treatment outcomes including overall survival (OS), event-free survival (EFS), relapse-free survival (RFS), complete remission (CR), and overall response rate (ORR) after therapy were extracted. Five studies comparing addition of FLT3 inhibitors and placebo or blank control to chemotherapy were analyzed in Part I, showing improved OS (hazard ratio [HR]=0.86, 95% confidence interval [CI]=0.75-0.99, P=0.03) in the FLT3 inhibitor group but without a significant improvement on EFS (HR=0.86, 95% CI=0.62-1.21, P=0.39) and ORR (odds ratio [OR]=1.10, 95% CI=0.89-1.35, P=0.38). Twenty-one studies evaluating the benefit of using FLT3 inhibitors in different FLT3-type AML patients were analyzed in Part II, showing that FLT3-internal tandem duplication (ITD)-positive patients were more sensitive to FLT3 inhibitor treatment and achieved better CR (OR=1.89, 95% CI=1.06-3.37, P=0.03) and ORR (OR=3.07, 95% CI=2.13-4.43, P<0.001). Conclusion: Our study showed that combined use of FLT3 inhibitors improved OS and that the FLT3 status of AML patients could affect their sensitivity to FLT3 inhibitors in terms of CR and ORR.