{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:58:38Z","timestamp":1785257918505,"version":"3.55.0"},"reference-count":26,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Haematol"],"abstract":"<jats:p>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\u20130.84; p &lt; 0.001) and PFS (HR: 0.73, 95% CI: 0.63\u20130.86; p &lt; 0.001). Subgroup analysis revealed that gilteritinib showed improvements in both OS (HR: 0.71, p = 0.001) and PFS (HR: 0.71, p &lt; 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 &lt; 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.<\/jats:p>","DOI":"10.1159\/000553180","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:00:47Z","timestamp":1781884847000},"page":"1-12","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of Second-Generation FLT3 Inhibitors in FLT3-Mutated AML: A Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.1159","author":[{"given":"Qili","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingni","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongtao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangshuo","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixian","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa074306"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v98.6.1752"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0420"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614359"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31041-9"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011583"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35746"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30150-0"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005038"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014586"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00464-6"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02474"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02382-9"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0876"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100905"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-693879"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-017-0470-z"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14539"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003398"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2020.1801637"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000572"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0357-9"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-1011"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016867"}],"container-title":["Acta Haematologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000553180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:00:45Z","timestamp":1785254445000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000553180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,19]]},"references-count":26,"URL":"https:\/\/doi.org\/10.1159\/000553180","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.32725854","asserted-by":"subject"}]},"ISSN":["0001-5792","1421-9662"],"issn-type":[{"value":"0001-5792","type":"print"},{"value":"1421-9662","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,19]]}}}