{"entity":{"id":"paper-admiral-gilteritinib-flt3-nejm-2019","kind":"paper","name":"ADMIRAL: gilteritinib pills versus chemotherapy for relapsed FLT3-mutated acute myeloid leukaemia","aka":[],"tldr":"An oral FLT3 inhibitor extended survival compared with salvage chemotherapy in relapsed AML with a FLT3 mutation, doubling the remission rate.","summary":"ADMIRAL randomised 371 adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to gilteritinib 120 mg daily or investigator-chosen salvage chemotherapy (high- or low-intensity). Primary endpoints were overall survival and the rate of complete remission or remission with partial haematological recovery. Median OS was 9.3 versus 5.6 months (hazard ratio 0.64) and one-year survival 37.1% versus 16.7%; CR/CRh was 34.0% versus 15.3%. More patients on gilteritinib proceeded to transplant, and toxicity was lower than with chemotherapy. It established single-agent targeted therapy as a standard in relapsed FLT3-mutated AML.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1902688"},{"label":"ClinicalTrials.gov NCT02421939","url":"https://clinicaltrials.gov/study/NCT02421939"}],"tags":[],"related":["paper-quantum-first-quizartinib-lancet-2023"],"cancers":["aml"],"sections":[],"technologies":["allogeneic-hsct"],"targets":["flt3"],"drugs":["gilteritinib","midostaurin","quizartinib"],"companies":["astellas"],"institutions":[],"pathways":[],"terms":["os"],"trials":["admiral"],"people":[],"bottlenecks":["b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1902688","authors":"Perl AE, Martinelli G, Cortes JE, et al.","paperType":"rct","findings":["371 patients with relapsed/refractory FLT3-mutated AML; gilteritinib vs salvage chemotherapy (2:1).","Median OS 9.3 vs 5.6 months; hazard ratio 0.64.","1-year overall survival 37.1% vs 16.7%.","CR/CRh 34.0% vs 15.3%; complete remission 21.1% vs 10.5%.","Fewer grade 3 or higher adverse events per exposure-adjusted analysis with gilteritinib."],"whatItMeans":"ADMIRAL showed that a targeted oral drug can beat chemotherapy outright in relapsed AML, and made gilteritinib the standard bridge to transplant for FLT3-mutated relapse. Its success also underpinned FLT3 inhibitor use in first-line combinations. Resistance through FLT3-independent clones and RAS pathway mutations limits durability without transplant.","caveats":["Modest absolute survival gain; most patients not transplanted eventually relapsed.","Open-label with heterogeneous chemotherapy comparators.","Excluded patients previously treated with certain FLT3 inhibitors; prior midostaurin exposure was uncommon.","Differentiation syndrome and QT prolongation require monitoring."],"changedPractice":true,"participants":371},"route":"/key-papers/paper-admiral-gilteritinib-flt3-nejm-2019/","neighbours":{"paper":[{"id":"paper-quantum-first-quizartinib-lancet-2023","kind":"paper","name":"QuANTUM-First: quizartinib added to intensive chemotherapy and continued as maintenance in newly diagnosed FLT3-ITD AML","route":"/key-papers/paper-quantum-first-quizartinib-lancet-2023/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-flt3","kind":"cancer","name":"FLT3-mutated acute myeloid leukaemia","route":"/cancers/aml-flt3/"}],"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"}],"target":[{"id":"flt3","kind":"target","name":"FLT3","route":"/targets/flt3/"}],"drug":[{"id":"gilteritinib","kind":"drug","name":"Gilteritinib","route":"/drugs/gilteritinib/"},{"id":"midostaurin","kind":"drug","name":"Midostaurin","route":"/drugs/midostaurin/"},{"id":"quizartinib","kind":"drug","name":"Quizartinib","route":"/drugs/quizartinib/"}],"company":[{"id":"astellas","kind":"company","name":"Astellas","route":"/companies/astellas/"}],"term":[{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"}],"trial":[{"id":"admiral","kind":"trial","name":"ADMIRAL","route":"/trials/admiral/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"alexander-perl","kind":"person","name":"Alexander E. Perl","route":"/people/alexander-perl/"}]}}