{"entity":{"id":"aml-flt3","kind":"cancer","name":"FLT3-mutated acute myeloid leukaemia","aka":["FLT3-ITD AML","FLT3-TKD AML","FLT3-positive AML"],"tldr":"FLT3-mutated acute myeloid leukaemia carries a mutation in a growth-signal receptor that makes the leukaemia relapse quickly. Adding a FLT3 blocker to chemotherapy, midostaurin or quizartinib, lengthens life, and gilteritinib is the standard when the disease comes back.","summary":"FLT3 is a receptor tyrosine kinase on blood stem cells. An internal tandem duplication (ITD) in about a quarter of adult AML, or a point mutation in the tyrosine kinase domain (TKD) in under a tenth, keeps it switched on. FLT3-ITD leukaemias present with high white counts and relapse early, and the ELN 2022 classification places them in the intermediate-risk group whatever the allelic ratio, so an allogeneic transplant in first remission is usually recommended. Testing for FLT3 must return within days because the inhibitor is started with the first chemotherapy cycle.\n\nRATIFY, reported in 2017, randomised 717 patients aged 18 to 59 to midostaurin or placebo added to 7+3 induction, consolidation and a year of maintenance: median overall survival rose from 25.6 to 74.7 months (hazard ratio 0.78), and midostaurin became the first targeted drug approved in AML that year. QuANTUM-First extended the approach to FLT3-ITD patients up to 75 with the more selective quizartinib: median survival 31.9 versus 15.1 months (hazard ratio 0.776), approved in 2023. For relapsed or refractory FLT3-mutated disease, ADMIRAL showed single-agent gilteritinib beat salvage chemotherapy, median survival 9.3 versus 5.6 months (hazard ratio 0.64), and it was approved in 2018.\n\nThe open questions are which inhibitor to pair with intensive chemotherapy, whether FLT3 inhibitor maintenance after transplant should be universal or MRD-guided (MORPHO found the gilteritinib benefit concentrated in patients with detectable FLT3-ITD before or after transplant), how to combine FLT3 inhibitors with venetoclax and azacitidine in unfit patients, and how to treat the resistance mutations and clonal switches that follow each drug.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/CD135","links":[{"label":"Wikipedia: FLT3","url":"https://en.wikipedia.org/wiki/CD135"},{"label":"NCCN Guidelines: Acute Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411"}],"tags":["subtype-page"],"related":["aml-idh","aml-npm1-kmt2a","aml-older-unfit","aml-secondary","aml-paediatric"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","ngs-mrd-clonoseq"],"targets":["flt3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["flt3-itd-allelic-ratio","eln-risk","seven-plus-three"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-admiral-gilteritinib-flt3-nejm-2019","paper-quantum-first-quizartinib-lancet-2023","paper-eln-2022-aml-dohner-blood-2022","paper-ratify-midostaurin-nejm-2017"],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"About three in ten adults with acute myeloid leukaemia carry a FLT3 mutation, most often the internal tandem duplication, which used to mark one of the worst outlooks in the disease.","subtypes":["FLT3-ITD AML (internal tandem duplication)","FLT3-TKD AML (D835 and other kinase domain point mutations)","FLT3-mutated AML with co-mutated NPM1"],"biomarkers":["FLT3-ITD and allelic ratio","FLT3-TKD (D835, I836)","NPM1 co-mutation","ELN 2022 risk group","FLT3-ITD MRD by NGS before and after transplant","Karyotype"],"standardOfCare":[{"setting":"Newly diagnosed, fit for intensive chemotherapy","approach":"7+3 induction with midostaurin (RATIFY) or, for FLT3-ITD, quizartinib (QuANTUM-First), then consolidation and maintenance with the same inhibitor; allogeneic transplant in first remission for most FLT3-ITD patients.","refs":["midostaurin","quizartinib","cytarabine-7-3","ratify","quantum-first","allogeneic-hsct","flt3i-plus-7-3"],"guideline":{"version":"NCCN Guidelines: Acute Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411"}},{"setting":"Newly diagnosed, unfit for intensive chemotherapy","approach":"Venetoclax plus azacitidine, with a FLT3 inhibitor added in trials or where labelled; gilteritinib with azacitidine is an option.","refs":["venetoclax","azacitidine","gilteritinib","viale-a"],"guideline":{"version":"NCCN Guidelines: Acute Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411"}},{"setting":"Relapsed or refractory","approach":"Gilteritinib alone (ADMIRAL) as a bridge to allogeneic transplant; quizartinib where approved for relapse; FLT3 inhibitor maintenance after transplant.","refs":["gilteritinib","admiral","quizartinib","allogeneic-hsct"],"guideline":{"version":"NCCN Guidelines: Acute Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411"}}],"stateOfArt":["A FLT3 inhibitor with 7+3 is standard for every newly diagnosed FLT3-mutated patient fit for chemotherapy; RATIFY roughly tripled median survival.","Gilteritinib turned relapsed FLT3-mutated AML from a chemotherapy-only setting into a targeted one.","Post-transplant FLT3 inhibitor maintenance is moving towards MRD-guided use."],"history":[{"year":1996,"title":"FLT3 internal tandem duplications described in AML","refs":["flt3"]},{"year":2017,"title":"RATIFY: midostaurin with 7+3 lengthens life; first targeted AML drug approved","refs":["ratify","midostaurin"]},{"year":2018,"title":"Gilteritinib approved for relapsed FLT3-mutated AML after ADMIRAL","refs":["admiral","gilteritinib"]},{"year":2022,"title":"ELN 2022 places all FLT3-ITD AML in intermediate risk","refs":["eln-risk"]},{"year":2023,"title":"QuANTUM-First: quizartinib approved for FLT3-ITD AML up to age 75","refs":["quantum-first","quizartinib"]}],"pipeline":["gilteritinib","quizartinib","venetoclax","myelomatch","ngs-mrd-clonoseq"],"openProblems":["Which FLT3 inhibitor to pair with intensive chemotherapy, and whether one inhibitor suits both ITD and TKD disease.","Whether post-transplant maintenance should be given to everyone or only to patients with detectable FLT3-ITD.","Resistance through FLT3 gatekeeper mutations and through loss of FLT3 dependence."],"parent":"aml"},"route":"/cancers/aml-flt3/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"},{"id":"aml-older-unfit","kind":"cancer","name":"Acute myeloid leukaemia in older or unfit patients","route":"/cancers/aml-older-unfit/"},{"id":"aml-idh","kind":"cancer","name":"IDH1- and IDH2-mutated acute myeloid leukaemia","route":"/cancers/aml-idh/"},{"id":"aml-npm1-kmt2a","kind":"cancer","name":"NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia","route":"/cancers/aml-npm1-kmt2a/"},{"id":"aml-secondary","kind":"cancer","name":"Secondary and therapy-related acute myeloid leukaemia","route":"/cancers/aml-secondary/"}],"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"ngs-mrd-clonoseq","kind":"technology","name":"NGS-based MRD (clonoSEQ and molecular MRD)","route":"/technologies/ngs-mrd-clonoseq/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"flt3","kind":"target","name":"FLT3","route":"/targets/flt3/"},{"id":"stat5","kind":"target","name":"STAT5 (STAT5A, STAT5B)","route":"/targets/stat5/"}],"term":[{"id":"seven-plus-three","kind":"term","name":"7+3 induction chemotherapy","route":"/terms/seven-plus-three/"},{"id":"eln-risk","kind":"term","name":"ELN 2022 risk classification","route":"/terms/eln-risk/"},{"id":"flt3-itd-allelic-ratio","kind":"term","name":"FLT3-ITD allelic ratio","route":"/terms/flt3-itd-allelic-ratio/"}],"paper":[{"id":"paper-admiral-gilteritinib-flt3-nejm-2019","kind":"paper","name":"ADMIRAL: gilteritinib pills versus chemotherapy for relapsed FLT3-mutated acute myeloid leukaemia","route":"/key-papers/paper-admiral-gilteritinib-flt3-nejm-2019/"},{"id":"paper-eln-2022-aml-dohner-blood-2022","kind":"paper","name":"ELN 2022: diagnosis and management of acute myeloid leukaemia in adults","route":"/key-papers/paper-eln-2022-aml-dohner-blood-2022/"},{"id":"paper-morpho-gilteritinib-levis-jco-2024","kind":"paper","name":"MORPHO: gilteritinib as post-transplant maintenance for FLT3-ITD acute myeloid leukaemia","route":"/key-papers/paper-morpho-gilteritinib-levis-jco-2024/"},{"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/"},{"id":"paper-ratify-midostaurin-nejm-2017","kind":"paper","name":"RATIFY: midostaurin added to chemotherapy for acute myeloid leukaemia with a FLT3 mutation","route":"/key-papers/paper-ratify-midostaurin-nejm-2017/"}],"trial":[{"id":"nct03182244","kind":"trial","name":"A Study of ASP2215 Versus Salvage Chemotherapy In Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase 3 (FLT3) Mutation","route":"/trials/nct03182244/"},{"id":"aaml1031","kind":"trial","name":"AAML1031","route":"/trials/aaml1031/"},{"id":"admiral","kind":"trial","name":"ADMIRAL","route":"/trials/admiral/"},{"id":"nct05586074","kind":"trial","name":"HEC73543 Versus Salvage Chemotherapy in R/R FLT3-ITD AML","route":"/trials/nct05586074/"},{"id":"morpho","kind":"trial","name":"MORPHO","route":"/trials/morpho/"},{"id":"myelomatch","kind":"trial","name":"myeloMATCH","route":"/trials/myelomatch/"},{"id":"quantum-first","kind":"trial","name":"QuANTUM-First","route":"/trials/quantum-first/"},{"id":"ratify","kind":"trial","name":"RATIFY (CALGB 10603)","route":"/trials/ratify/"},{"id":"nct03793478","kind":"trial","name":"Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood","route":"/trials/nct03793478/"},{"id":"viale-a","kind":"trial","name":"VIALE-A","route":"/trials/viale-a/"}],"drug":[{"id":"azacitidine","kind":"drug","name":"Azacitidine","route":"/drugs/azacitidine/"},{"id":"cytarabine-7-3","kind":"drug","name":"Cytarabine + anthracycline ('7+3')","route":"/drugs/cytarabine-7-3/"},{"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/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"pairing":[{"id":"flt3i-plus-7-3","kind":"pairing","name":"FLT3 inhibitor + intensive chemotherapy","route":"/pairings/flt3i-plus-7-3/"}],"biomarker":[{"id":"flt3-itd","kind":"biomarker","name":"FLT3-ITD (internal tandem duplication)","route":"/biomarkers/flt3-itd/"},{"id":"flt3-tkd","kind":"biomarker","name":"FLT3-TKD (D835 and I836 tyrosine kinase domain mutations)","route":"/biomarkers/flt3-tkd/"}]}}