The impact of different FLT3-inhibitors on overall survival of de novo acute myeloid leukemia: A network meta-analysis

Leuk Res. 2024 Sep:144:107549. doi: 10.1016/j.leukres.2024.107549. Epub 2024 Jul 17.

Abstract

FLT3 inhibitors combined with chemotherapy are the standard of care for newly diagnosed FLT3-mutated acute myeloid leukemia (AML). However, no head-to-head studies have established the superiority of one FLT3 inhibitor over another. We conducted a network meta-analysis (NMA) to evaluate overall survival (OS) among different FLT3 inhibitors. Three relevant randomized controlled trials (RCTs), involving 1.358 patients treated with midostaurin, quizartinib, and sorafenib, were included in our analysis. The hazard ratios (HRs) revealed no significant differences in OS between midostaurin and quizartinib (HR, 1.00; 95 % CI, 0.73-1.36), midostaurin and sorafenib (HR, 0.97; 95 % CI, 0.52-1.84), or quizartinib and sorafenib (HR, 0.97; 95 % CI, 0.51-1.85). This NMA, the first to explore this issue, found no OS differences among the different FLT3 inhibitors. In the absence of direct comparison trials, our findings provide practical insights for clinical decision-making.

Keywords: Acute myeloid leukemia; FLT3 inhibitors; Head-to-head studies; Network meta-analysis.

Publication types

  • Network Meta-Analysis

MeSH terms

  • Benzothiazoles / pharmacology
  • Benzothiazoles / therapeutic use
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / mortality
  • Phenylurea Compounds
  • Protein Kinase Inhibitors* / therapeutic use
  • Randomized Controlled Trials as Topic
  • Sorafenib* / therapeutic use
  • Staurosporine* / analogs & derivatives
  • Staurosporine* / therapeutic use
  • Survival Rate
  • fms-Like Tyrosine Kinase 3* / antagonists & inhibitors
  • fms-Like Tyrosine Kinase 3* / genetics

Substances

  • Benzothiazoles
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • midostaurin
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • quizartinib
  • Sorafenib
  • Staurosporine