{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:06:26Z","timestamp":1793048786878,"version":"4.5.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Blueprint Medicines Corporation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Advanced systemic mastocytosis (AdvSM) is a rare,\n                    <jats:italic>KIT<\/jats:italic>\n                    D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of a prespecified interim analysis of an ongoing pivotal single-arm phase\u20092 trial (no.\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03580655\">NCT03580655<\/jats:ext-link>\n                    ) of avapritinib, a potent, selective KIT D816V inhibitor administered primarily at a once-daily starting dose of 200\u2009mg in patients with AdvSM (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200962). The primary endpoint was overall response rate (ORR). Secondary endpoints included mean baseline change in AdvSM\u2013Symptom Assessment Form Total Symptom Score and quality of life, time to response, duration of response, progression-free survival, overall survival, changes in measures of disease burden and safety. The primary endpoint was successfully met (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20091.6\u2009\u00d7\u200910\n                    <jats:sup>-9<\/jats:sup>\n                    ), with an ORR of 75% (95% confidence interval 57\u201389) in 32\u2009response-evaluable patients with AdvSM who had sufficient follow-up for response assessment, including 19% with complete remission with full or partial hematologic recovery. Reductions of \u226550% from baseline in serum tryptase (93%), bone marrow mast cells (88%) and\n                    <jats:italic>KIT<\/jats:italic>\n                    D816V variant allele fraction (60%) were observed. The most frequent grade\u2009\u22653 adverse events were neutropenia (24%), thrombocytopenia (16%) and anemia (16%). Avapritinib demonstrated a high rate of clinical, morphological and molecular responses and was generally well tolerated in patients with AdvSM.\n                  <\/jats:p>","DOI":"10.1038\/s41591-021-01539-8","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T12:03:15Z","timestamp":1638792195000},"page":"2192-2199","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":153,"title":["Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8253-6156","authenticated-orcid":false,"given":"Jason","family":"Gotlib","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepti H.","family":"Radia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-1331","authenticated-orcid":false,"given":"Michael W.","family":"Deininger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5478-7847","authenticated-orcid":false,"given":"Tracy I.","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Panse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro M.","family":"Vannucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Platzbecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Alvarez-Twose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Mital","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Hermine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingunn","family":"Dybedal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-4060","authenticated-orcid":false,"given":"Elizabeth O.","family":"Hexner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa K.","family":"Hicks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lambert","family":"Span","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Mesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4343-5712","authenticated-orcid":false,"given":"Prithviraj","family":"Bose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen M.","family":"Pettit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L.","family":"Heaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8564-5400","authenticated-orcid":false,"given":"Stephen T.","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayita","family":"Sen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Min","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenton G.","family":"Mar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7865-2306","authenticated-orcid":false,"given":"Daniel J.","family":"DeAngelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"1539_CR1","doi-asserted-by":"publisher","first-page":"eaao1690","DOI":"10.1126\/scitranslmed.aao1690","volume":"9","author":"EK Evans","year":"2017","unstructured":"Evans, E. 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He has received research funding, is the co-chair of the phase\u20092 trial of ripretinib in AdvSM Study Steering Committee and has honoraria for these roles and serves on advisory boards for Deciphera. He also serves as Chair of the Central Response Review Committee for the phase\u20092 trial of bezuclastinib in AdvSM. A.R. has been a clinical advisory board\/study steering committee member (PATHFINDER trial) and received honoraria and funding to cover travel expenses from Blueprint Medicines Corporation. He has received advisory board fees, speaking fees and travel support from Novartis, Deciphera, Incyte, Celgene, AOP Pharmaceuticals and AbbVie, and research support from Novartis. D.H.R. has been a clinical advisory board\/study steering committee member (EXPLORER and PATHFINDER studies) for Blueprint Medicines Corporation, and was involved with educational events and advisory boards for Novartis. M.W.D. has received honorarium fees from Blueprint Medicines Corporation, Incyte, Medscape, Sangamo and Takeda; consultancy fees from Blueprint Medicines Corporation, DisperSol, Fusion Pharma, Novartis and Sangamo; and research funding from Blueprint Medicines Corporation, Incyte, Leukemia & Lymphoma Society, Novartis, Pfizer, SPARC and Takeda. He is part of Study Steering Committees for Blueprint Medicines Corporation and Takeda and is a case author for Medscape. T.I.G. has been a clinical advisory board\/study steering committee member (EXPLORER and PATHFINDER studies) and has received consulting fees from Blueprint Medicines Corporation, Celgene and Incyte. J.P. has received honorarium fees from Apellis, Blueprint Medicines Corporation, BMS, Gr\u00fcnenthal, MSD, Sobi and F. Hoffmann-La Roche. He has served on the speaker\u2019s bureau of Alexion, Boehringer Ingelheim, Novartis, Pfizer and Chugai. A.M.V. has participated in speakers\u2019 bureaux for AOP, BMS-Celgene, Novartis and Shire, and on advisory boards for AbbVie, BMS-Celgene, CTI BioPharma, Incyte and Novartis. U.P. received research funding from BMS, Amgen, Novartis, Curis and BerGenBio. I.A.-T. has served on advisory boards for, and received honoraria and research funding from, Blueprint Medicines Corporation and has participated in educational events for Novartis. A.M. has received honorarium fees from Takeda, Pfizer, Novo Nordisk, Behring, AbbVie, Novartis, Cilag, Janssen and Bayer. O.H. received research funding from AB Science, BMS\/Celgene, Alexion, Novartis and Inatherys, consulted for AB Science and is a shareholder for AB Science. I.D. has received advisory board fees from Novartis. E.O.H. has received research support (institution) from Blueprint Medicines Corporation, Samus Therapeutics and Novartis Oncology. She serves on a data safety monitoring committee for Blueprint Medicines Corporation and is a member of the hematology exam committee for the American Board of Internal Medicine. L.K.H. has received research support (institution) from Gilead Sciences. L.S. has no disclosures. R.M. has been a consultant for Novartis, Sierra Oncology and La Jolla Pharma and has received research support from Celgene, Incyte, AbbVie, Samus, Genentech, Promedior and CTI BioPharma. P.B. has received research support from Incyte, Celgene (now BMS), CTI BioPharma, Kartos, Blueprint Medicines Corporation, Constellation, Astellas, Pfizer, NS Pharma and Promedior; and honoraria from Incyte, Celgene (now BMS), CTI BioPharma, Kartos and Blueprint Medicines Corporation. K.M.P. has participated on advisory boards for CTI BioPharma, PharmaEssentia and Kura Oncology. M.L.H. has received research funding from Blueprint Medicines Corporation, BMS, CTI BioPharma, Deciphera, Incyte, Novartis and Sierra Oncology; and consulting fees from AbbVie, CTI BioPharma, Novartis, Blueprint Medicines Corporation and Partner Therapeutics. S.T.O. has been a consultant for Gilead Sciences, Novartis, Kartos Therapeutics, CTI BioPharma, Celgene\/Bristol Myers Squibb, Disc Medicine, Blueprint Medicines Corporation, PharmaEssentia, Constellation and Incyte. J.S., H.-M.L. and B.G.M. are employees and\/or equity holders of Blueprint Medicines Corporation. D.J.D. has been a clinical advisory board\/study steering committee member (EXPLORER and PATHFINDER studies) for Blueprint Medicines Corporation. He has served as a consultant for Amgen, Agios, Autolus, Forty-Seven, Incyte Corporation, Jazz, Novartis, Pfizer, Shire and Takeda; and has received research funding from AbbVie, GlycoMimetics and Novartis.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}