{"entity":{"id":"midostaurin","kind":"drug","name":"Midostaurin","aka":[],"tldr":"The first drug to improve survival in FLT3-mutated AML, added to standard chemotherapy: median survival went from about two years to more than six.","summary":"RATIFY (n=717, FLT3-ITD or TKD, age 18-59): midostaurin with 7+3 and as maintenance improved OS (median 74.7 vs 25.6 months, HR 0.78). Approved 2017 for newly diagnosed FLT3-mutated AML and for systemic mastocytosis. Now being displaced in FLT3-ITD by quizartinib (QuANTUM-First) and challenged by gilteritinib in frontline trials; still the only option labelled for FLT3-TKD.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Midostaurin","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Midostaurin"}],"tags":[],"related":["flt3-itd","flt3-tkd"],"cancers":["aml","systemic-mastocytosis","aml-flt3","advanced-systemic-mastocytosis"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["flt3","kit"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["ratify","nct03591510"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Rydapt","modality":"Small-molecule multikinase inhibitor (FLT3)","mechanism":"Type I multikinase inhibitor of FLT3 (ITD and TKD), KIT, PDGFR, VEGFR2, and PKC.","approvals":[{"region":"US","year":2017,"indication":"Newly diagnosed FLT3-mutated AML with 7+3 and consolidation; advanced systemic mastocytosis"}],"mechanismSteps":["Midostaurin binds the active conformation of FLT3","Constitutive FLT3-ITD/TKD signalling through STAT5, RAS/MAPK and PI3K stops","Blast proliferation halts and apoptosis resumes","Given with 7+3 during induction and consolidation, then 12 months of maintenance"],"dosing":{"route":"Oral","schedule":"50 mg twice daily on days 8-21 of each induction and consolidation cycle, then 50 mg twice daily continuously for up to 12 cycles of maintenance","monitoring":"QT interval, pulmonary symptoms, counts","source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Rydapt"},"toxicity":[{"event":"Febrile neutropenia","grade3PlusPct":84,"source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Rydapt","note":"Both arms of RATIFY; not drug-specific"},{"event":"Nausea","anyGradePct":83},{"event":"Rash/desquamation","grade3PlusPct":14},{"event":"QT prolongation","note":"Monitor; avoid strong CYP3A4 inhibitors where possible"}],"access":[],"regulatoryEvents":[{"date":"2017-04-28","type":"approval","region":"US","note":"First FLT3 inhibitor approved"}]},"route":"/drugs/midostaurin/","neighbours":{"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/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-older-unfit","kind":"cancer","name":"Acute myeloid leukaemia in older or unfit patients","route":"/cancers/aml-older-unfit/"},{"id":"advanced-systemic-mastocytosis","kind":"cancer","name":"Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)","route":"/cancers/advanced-systemic-mastocytosis/"},{"id":"aml-flt3","kind":"cancer","name":"FLT3-mutated acute myeloid leukaemia","route":"/cancers/aml-flt3/"},{"id":"systemic-mastocytosis","kind":"cancer","name":"Systemic mastocytosis","route":"/cancers/systemic-mastocytosis/"}],"technology":[{"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":"kit","kind":"target","name":"KIT","route":"/targets/kit/"},{"id":"pkc","kind":"target","name":"Protein kinase C family (PKC)","route":"/targets/pkc/"},{"id":"stat5","kind":"target","name":"STAT5 (STAT5A, STAT5B)","route":"/targets/stat5/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"trial":[{"id":"nct03591510","kind":"trial","name":"A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML","route":"/trials/nct03591510/"},{"id":"ratify","kind":"trial","name":"RATIFY (CALGB 10603)","route":"/trials/ratify/"}],"pairing":[{"id":"flt3i-plus-7-3","kind":"pairing","name":"FLT3 inhibitor + intensive chemotherapy","route":"/pairings/flt3i-plus-7-3/"}],"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-gotlib-midostaurin-advanced-systemic-mastocytosis-nejm-2016","kind":"paper","name":"Efficacy and safety of midostaurin in advanced systemic mastocytosis","route":"/key-papers/paper-gotlib-midostaurin-advanced-systemic-mastocytosis-nejm-2016/"},{"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/"}],"term":[{"id":"seven-plus-three","kind":"term","name":"7+3 induction chemotherapy","route":"/terms/seven-plus-three/"}],"pathway":[{"id":"aml-signalling","kind":"pathway","name":"Acute myeloid leukaemia (KEGG map)","route":"/pathways/aml-signalling/"}]}}