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Accurate assessment and prediction of clinical course and disease outcome before and during treatment with the KIT inhibitors midostaurin and avapritinib may facilitate optimization of treatment strategies. We retrospectively evaluated clinical, morphologic, laboratory, and genetic predictors of outcome in 79 midostaurin- and 176 avapritinib-treated patients. The number of mutations at baseline in\n                    <jats:italic>SRSF2<\/jats:italic>\n                    \/\n                    <jats:italic>ASXL1<\/jats:italic>\n                    \/\n                    <jats:italic>EZH2<\/jats:italic>\n                    (midostaurin) and in\n                    <jats:italic>SRSF2\/RUNX1\/SETBP1<\/jats:italic>\n                    (avapritinib) delineated highly predictive 3-tier risk classification systems. Treatment with avapritinib was associated with an early response of the\n                    <jats:italic>KIT<\/jats:italic>\n                    D816V variant allele frequency; a\u2009\u226510% reduction in peripheral blood at day 15 indicated improved overall survival (OS). Within 3 months of starting treatment, a\u2009\u226525% increase in alkaline phosphatase (AP) levels (AP flare) was observed in 46\/47% of midostaurin\/avapritinib-treated patients and was associated with longer OS. Multivariable analyses identified a\u2009\u226525% reduction in the\n                    <jats:italic>KIT<\/jats:italic>\n                    D816V allele burden (midostaurin), normalization of serum albumin levels (avapritinib), and normalization of hemoglobin and\/or platelet levels (midostaurin and avapritinib) within 6 months as significant predictors for prolonged OS. In conclusion, genetic profiling, dynamic laboratory parameters, and\n                    <jats:italic>KIT<\/jats:italic>\n                    D816V monitoring improve outcome prediction in patients with AdvSM on midostaurin or avapritinib.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-03149-0","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:06:15Z","timestamp":1791536775000},"page":"2562-2572","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predicting the clinical course of advanced systemic mastocytosis on treatment with avapritinib or midostaurin"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-1504","authenticated-orcid":false,"given":"Johannes","family":"L\u00fcbke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Gotlib","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"}]},{"given":"Juliana","family":"Schwaab","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","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":"Ilda","family":"Bidollari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u0161a","family":"Dimitrijevi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier I.","family":"Mu\u00f1oz-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-6507","authenticated-orcid":false,"given":"Andreas","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"3149_CR1","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","volume":"36","author":"JD Khoury","year":"2022","unstructured":"Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. 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JG has received research funding from, is the co-chair of the Study Steering Committee for, and has honoraria for these roles and serves on advisory boards for Deciphera; and is Chair of the Response Adjudication Committee, has received research funding from, served on advisory boards for, and received honoraria and funding to cover travel expenses from Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi. DDA has served as a consultant for Agios, Amgen, Autolus, Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi, Forty-Seven, Gilead, Incyte Corporation, Jazz, Novartis, Pfizer, Servier, and Takeda; and has received research funding from AbbVie, Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi, GlycoMimetics, and Novartis. JS has received honoraria from AbbVie, AOP, AstraZeneca, Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi, Cogent Biosciences, GSK, and Novartis; and received consultancy fees from AstraZeneca, Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi, GSK, and Novartis. DHR has been a clinical advisory board\/study steering group member (EXPLORER\/PATHFINDER) for, was involved in educational events for, and received research funding from Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi; was involved with educational events and advisory boards for Novartis; and is a Steering Committee member for APEX study\u2014Cogent Biosciences. MD has received honoraria fees from Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi, Incyte, Medscape, Sangamo, and Takeda; received consultancy fees from Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi, DisperSol, Fusion Pharma, Novartis, and Sangamo; received research funding from Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi, Incyte, Leukemia & Lymphoma Society, Novartis, Pfizer, SPARC, and Takeda; is part of a study management committee for Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi and Takeda; is a case author for Medscape; is Executive Vice President and Chief Scientific Officer, Versiti; is Director and Senior Investigator, Versiti Blood Research Institute; and is Professor, Division of Hematology and Oncology, Department of Medicine, and Associate Dean for Research, Medical College of Wisconsin. TIG is President, Innovation Business Unit, and Chief Scientific Officer of ARUP Laboratories, a nonprofit company owned by the University of Utah; and has received consulting fees from Beckman Coulter, Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi, BMS\/Celgene, Cogent Biosciences, and Incyte. IB, SD, and HS are currently employees of Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi. JIMG is an employee and equity holder of Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi. AR has received research funding from, served on advisory boards for, and received honoraria and funding to cover travel expenses from AbbVie, AOP, Blueprint Medicines Corporation, Cambridge, MA, a wholly owned subsidiary of Sanofi, BMS, GSK, Incyte, and Novartis.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}