Prevalence of Fms-Like Tyrosine Kinase 3 (FLT3) Mutations in Patients With Acute Myeloid Leukaemia: A Systematic Literature Review and Meta-Analysis

Background

Fms-like tyrosine kinase 3 (FLT3) mutations are associated with poor prognosis in patients with acute myeloid leukaemia (AML).

Aims

We conducted a systematic literature review and meta-analyses of studies reporting FLT3 mutation prevalence in patients with AML.

Materials & Methods

We searched all publications through September 2022; the earliest publication we retrieved was published in 1997. Based on these publications, data from the studies were generated between 1985 and 2021. Prevalence was evaluated overall and by study type, geographic location of study, patient age, and gender.

Results

Weighted mean (95% confidence interval) prevalence for FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain (TKD) mutations were 20% (19%–22%) and 7% (6%–8%), respectively, with wide variability in individual study estimates (FLT3-ITD: 5.1%–41.4%; FLT3-TKD: 2.3%–12.0%). Weighted mean prevalence estimates for FLT3-ITD and FLT3-TKD mutations were higher in populations from interventional (FLT3-ITD: 22%; FLT3-TKD: 8%) than non-interventional studies (FLT3-ITD: 19%; FLT3-TKD: 6%). Weighted mean FLT3 mutation prevalence estimates were higher for Europe (FLT3-ITD: 23%; FLT3-TKD: 8%) and lower for Asia (FLT3-ITD: 18%; FLT3-TKD: 5%). Weighted mean prevalence of FLT3-ITD mutations was higher in younger adults (aged 18–59 years; 23%) than paediatric (aged < 18 years; 12%) or older (aged ≥ 60 years; 18%) populations, and in females (22%) than males (18%).

Discussion

This was the first study to comprehensively assess the reported prevalence of FLT3 mutations worldwide among AML patients.

Conclusion

We described the distribution of FLT3 mutations; further work is needed to understand prevalence estimate heterogeneity.