FLT3 inhibitors in acute myeloid leukemia: A network meta-analysis of phase III trials
Abstract
e18505
Background:
FLT3 inhibitors improve outcomes in FLT3-mutated acute myeloid leukemia (AML); however, no head-to-head phase III comparisons exist among available agents. Updated randomized data from RATIFY (midostaurin), QUANTUM-First (quizartinib), and ADMIRAL (gilteritinib) enable indirect comparative effectiveness assessment of FLT3-directed therapy across treatment settings.
Methods:
A frequentist network meta-analysis was performed using phase III randomized trials enrolling FLT3-mutated AML patients. Reported hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS) were extracted. Random-effects network models estimated treatment effects versus chemotherapy and ranking probabilities (P-scores). The evidence network was anchored through shared chemotherapy control arms. Frontline survival comparisons included RATIFY and QUANTUM-First; ADMIRAL was analyzed separately due to relapse/refractory (R/R) population differences.
Results:
Across five comparisons (~1,600 patients), midostaurin (HR 0.78; 95% CI 0.63–0.96) and quizartinib (HR 0.78; 95% CI 0.62–0.98) each significantly reduced mortality versus placebo in frontline AML. Indirect comparison demonstrated no detectable difference between the two agents (HR 1.00; 95% CI 0.73–1.36). Ranking analysis assigned near-identical P-scores to midostaurin and quizartinib (0.74 vs 0.74), supporting equivalent likelihood of benefit in the frontline setting. In the R/R population, gilteritinib significantly…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,600 participants or records.
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