{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:06:14Z","timestamp":1790744774289,"version":"4.1.0"},"reference-count":60,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,2,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Midostaurin was a prototype kinase inhibitor, originally developed as a protein kinase C inhibitor and subsequently as an angiogenesis inhibitor, based on its inhibition of vascular endothelial growth factor receptor. Despite promising preclinical data, early clinical trials in multiple diseases showed only modest efficacy. In 1996, the relatively frequent occurrence of fms-like tyrosine kinase 3 (FLT3) activating mutations in acute myeloid leukemia (AML) was first recognized. Several years later, midostaurin was discovered to be a potent inhibitor of the FLT3 tyrosine kinase and to have activity against mutant forms of KIT proto-oncogene receptor tyrosine kinase, which drive advanced systemic mastocytosis (SM). Through a series of collaborations between industry and academia, midostaurin in combination with standard chemotherapy was evaluated in the Cancer and Leukemia Group B 10603\/RATIFY study, a large, phase 3, randomized, placebo-controlled trial in patients with newly diagnosed FLT3-mutated AML. This was the first study to show significant improvements in overall survival and event-free survival with the addition of a targeted therapy to standard chemotherapy in this population. Around the same time, durable responses were also observed in other trials of midostaurin in patients with advanced SM. Collectively, these clinical data led to the approval of midostaurin by the US Food and Drug Administration and the European Medicines Agency for both newly diagnosed FLT3-mutated AML and advanced SM.<\/jats:p>","DOI":"10.1182\/bloodadvances.2017011080","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T20:35:12Z","timestamp":1519763712000},"page":"444-453","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":151,"title":["Midostaurin: its odyssey from discovery to approval for treating acute myeloid leukemia and advanced systemic mastocytosis"],"prefix":"10.1182","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7526-2633","authenticated-orcid":false,"given":"Richard M.","family":"Stone","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul 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