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Although FLT3 inhibitors (FLT3is) combined with chemotherapy improve responses, long-term survival remains limited, and the optimal first-line strategy is unclear. We conducted a Bayesian network meta-analysis of eight randomized trials, including 1,793 patients, to compare treatment used in patietne eligible for intensive chemoteherapy for overall survival (OS). Treatments studied were 3\u2009+\u20097 with midostaurin, quizartinib, sorafenib, gemtuzumab ozogamicin (GO), glasdegib, CPX-351, and decitabine. FLT3i-based regimens improved outcomes but showed attenuated effects in this analysis, consistent with prior data. The small population with FLT3 mutation treated with GO\u2009+\u20093\u2009+\u20097 and CPX-351 provided good outcomes (SUCRA 86.1% and 71.7%), while glasdegib\u2009+\u20093\u2009+\u20097 and decitabine resulted in less effective strategies. Notably, 3\u2009+\u20097\u2009+\u2009GO showed superior benefit despite limited FLT3mut subgroup evidence. Ongoing studies are exploring CPX-351, GO, and FLT3i combinations, as well as novel strategies. Prospective, mutation-specific trials are needed to define optimal therapy.<\/jats:p>","DOI":"10.1007\/s00277-026-06948-8","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T08:33:19Z","timestamp":1775464399000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative efficacy of different therapeutic approaches in treatment na\u00efve FLT3-mutated AML eligible for intensive chemotherapy: a Bayesian network meta-analysis of randomized trials"],"prefix":"10.1007","volume":"105","author":[{"given":"Antonella","family":"Bruzzese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Lofaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica Antonia","family":"Martino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Mendicino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Labanca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santino","family":"Caserta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Lucia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Olivito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Amodio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fortunato","family":"Morabito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Vigna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Gentile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"issue":"11","key":"6948_CR1","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1182\/blood.2022015850","volume":"140","author":"DA Arber","year":"2022","unstructured":"Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka HM, Wang SA, Bagg A, Barbui T, Branford S, Bueso-Ramos CE, Cortes JE, Dal Cin P, DiNardo CD, Dombret H, Duncavage EJ, Ebert BL, Estey EH, Facchetti F, Foucar K, Gangat N, Gianelli U, Godley LA, G\u00f6kbuget N, Gotlib J, Hellstr\u00f6m-Lindberg E, Hobbs GS, Hoffman R, Jabbour EJ, Kiladjian JJ, Larson RA, Le Beau MM, Loh ML, L\u00f6wenberg B, Macintyre E, Malcovati L, Mullighan CG, Niemeyer C, Odenike OM, Ogawa S, Orfao A, Papaemmanuil E, Passamonti F, Porkka K, Pui CH, Radich JP, Reiter A, Rozman M, Rudelius M, Savona MR, Schiffer CA, Schmitt-Graeff A, Shimamura A, Sierra J, Stock WA, Stone RM, Tallman MS, Thiele J, Tien HF, Tzankov A, Vannucchi AM, Vyas P, Wei AH, Weinberg OK, Wierzbowska A, Cazzola M, D\u00f6hner H, Tefferi A (2022) International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. 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