Efficacy of Second-Generation FLT3 Inhibitors in FLT3-Mutated AML: A Meta-Analysis of Randomized Controlled Trials.

IF 2.8 4区医学 Q3 HEMATOLOGY

Acta Haematologica Pub Date : 2026-06-19 DOI:10.1159/000553180

Qili Yu, Jingni Cao, Yixia Chen, Xiongtao Ma, Kangshuo Hu, Yixian Qiu

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引用次数: 0

Abstract

Introduction: Second-generation FLT3 inhibitors have demonstrated clinical efficacy in FLT3-mutated acute myeloid leukemia (AML), although results across randomized trials remain inconsistent. This meta-analysis aimed to evaluate the efficacy of second-generation FLT3 inhibitors in patients with FLT3-mutated AML.

Methods: We systematically searched databases including PubMed, Web of Science, and the Cochrane Library (from inception to August 2025) to identify randomized controlled trials (RCTs) evaluating second-generation FLT3 inhibitors for treating FLT3-mutated AML. The primary endpoints were overall survival (OS) and progression-free survival (PFS). A random-effects model was used to calculate pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs). The study protocol was registered in PROSPERO (CRD420251132477).

Results: This meta-analysis included eight RCTs involving 2,231 patients. The second-generation FLT3 inhibitors evaluated were gilteritinib and quizartinib, and control treatments included placebo or active non-FLT3-inhibitor regimens. Patients treated with second-generation FLT3 inhibitors exhibited significant improvements in both OS (HR: 0.72, 95% CI: 0.62-0.84; p < 0.001) and PFS (HR: 0.73, 95% CI: 0.63-0.86; p < 0.001). Subgroup analysis revealed that gilteritinib showed improvements in both OS (HR: 0.71, p = 0.001) and PFS (HR: 0.71, p < 0.001), and quizartinib significantly improved OS (HR: 0.72, p = 0.013) with no significant difference in PFS (HR: 0.75, p = 0.142). Among patients with newly diagnosed AML, second-generation FLT3 inhibitors did not significantly improve PFS (HR: 0.73, p = 0.127) but significantly improved OS (HR: 0.80, p = 0.037). Among patients with relapsed/refractory AML, significant benefits were observed in both OS (HR: 0.67, p < 0.001) and PFS (HR: 0.74, p = 0.04). Benefits were observed across both placebo-controlled and active-comparator trials.

Conclusion: Second-generation FLT3 inhibitors significantly improve survival outcomes in FLT3-mutated AML, particularly for gilteritinib and in relapsed/refractory disease. Further studies are needed to clarify mutation subtype-specific and dose-specific effects.

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第二代FLT3抑制剂治疗FLT3突变AML的疗效：一项随机对照试验的meta分析

背景：第二代FLT3抑制剂已证明对FLT3突变的急性髓性白血病（AML）有临床疗效，尽管随机试验的结果仍不一致。本荟萃分析旨在评估第二代FLT3抑制剂对FLT3突变AML患者的疗效。方法：我们系统地检索了PubMed、Web of Science和Cochrane Library等数据库（从成立到2025年8月），以确定评估第二代FLT3抑制剂治疗FLT3突变AML的随机对照试验（rct）。主要终点是总生存期（OS）和无进展生存期（PFS）。采用随机效应模型计算合并风险比（hr）及其95%置信区间（95% ci）。该研究方案已在PROSPERO注册（CRD420251132477）。结果：本荟萃分析纳入8项随机对照试验，涉及2231例患者。评估的第二代FLT3抑制剂是吉特替尼和奎兹替尼，对照治疗包括安慰剂或活性非FLT3抑制剂方案。结论：第二代FLT3抑制剂显著改善了FLT3突变AML患者的生存结局，尤其是吉特替尼和复发/难治性疾病患者。需要进一步的研究来阐明突变亚型特异性和剂量特异性效应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Haematologica 医学-血液学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Acta Haematologica'' is a well-established and internationally recognized clinically-oriented journal featuring balanced, wide-ranging coverage of current hematology research. A wealth of information on such problems as anemia, leukemia, lymphoma, multiple myeloma, hereditary disorders, blood coagulation, growth factors, hematopoiesis and differentiation is contained in first-rate basic and clinical papers some of which are accompanied by editorial comments by eminent experts. These are supplemented by short state-of-the-art communications, reviews and correspondence as well as occasional special issues devoted to ‘hot topics’ in hematology. These will keep the practicing hematologist well informed of the new developments in the field.