{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:27:11Z","timestamp":1791487631745,"version":"4.3.4"},"reference-count":53,"publisher":"American Society of Hematology","issue":"15","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Avapritinib, a highly selective inhibitor of KIT D816V, was approved by the Food and Drug Administration in 2021 for treatment of advanced systemic mastocytosis (AdvSM) and by the European Medicines Agency in 2022 for AdvSM after prior systemic therapy. The phase 1 EXPLORER and phase 2 PATHFINDER trials demonstrated that avapritinib can elicit complete and durable clinical responses and molecular remission of KIT D816V. Key management challenges relate to the complex mutational landscape of AdvSM, often found with an associated hematologic neoplasm.<\/jats:p>","DOI":"10.1182\/blood.2021014612","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T15:05:54Z","timestamp":1658761554000},"page":"1667-1673","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":40,"title":["Avapritinib for advanced systemic mastocytosis"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8253-6156","authenticated-orcid":false,"given":"Jason","family":"Gotlib","sequence":"first","affiliation":[{"name":"1Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-6507","authenticated-orcid":false,"given":"Andreas","family":"Reiter","sequence":"additional","affiliation":[{"name":"2Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7865-2306","authenticated-orcid":false,"given":"Daniel J.","family":"DeAngelo","sequence":"additional","affiliation":[{"name":"3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"7","key":"2022101315372740800_bib1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0145-2126(01)00038-8","article-title":"Diagnostic criteria and classification of mastocytosis: a consensus proposal","volume":"25","author":"Valent","year":"2001","journal-title":"Leuk Res"},{"issue":"20","key":"2022101315372740800_bib2","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"2022101315372740800_bib3","first-page":"61","volume-title":"World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Horny","year":"2017"},{"issue":"11","key":"2022101315372740800_bib4","doi-asserted-by":"crossref","first-page":"e646","DOI":"10.1097\/HS9.0000000000000646","article-title":"Updated diagnostic criteria and classification of mast cell disorders: a consensus proposal","volume":"5","author":"Valent","year":"2021","journal-title":"HemaSphere"},{"issue":"23","key":"2022101315372740800_bib5","doi-asserted-by":"crossref","first-page":"5727","DOI":"10.1182\/blood-2009-02-205237","article-title":"Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors","volume":"113","author":"Lim","year":"2009","journal-title":"Blood"},{"issue":"18","key":"2022101315372740800_bib6","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1182\/blood-2009-05-220145","article-title":"Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies","volume":"114","author":"Pardanani","year":"2009","journal-title":"Blood"},{"issue":"16","key":"2022101315372740800_bib7","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1182\/blood.2019000932","article-title":"New developments in diagnosis, prognostication, and treatment of advanced systemic mastocytosis","volume":"135","author":"Reiter","year":"2020","journal-title":"Blood"},{"issue":"1","key":"2022101315372740800_bib8","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1182\/asheducation-2018.1.127","article-title":"The new tool \u201cKIT\u201d in advanced systemic mastocytosis","volume":"2018","author":"Shomali","year":"2018","journal-title":"Hematology (Am Soc Hematol Educ Program)"},{"issue":"4","key":"2022101315372740800_bib9","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/ajh.26118","article-title":"Systemic mastocytosis in adults: 2021 Update on diagnosis, risk stratification and management","volume":"96","author":"Pardanani","year":"2021","journal-title":"Am J Hematol"},{"issue":"12","key":"2022101315372740800_bib10","doi-asserted-by":"crossref","first-page":"e638","DOI":"10.1016\/S2352-3026(19)30166-8","article-title":"International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study","volume":"6","author":"Sperr","year":"2019","journal-title":"Lancet Haematol"},{"issue":"21","key":"2022101315372740800_bib11","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1182\/bloodadvances.2018026245","article-title":"Mayo alliance prognostic system for mastocytosis: clinical and hybrid clinical-molecular models","volume":"2","author":"Pardanani","year":"2018","journal-title":"Blood Adv"},{"issue":"31","key":"2022101315372740800_bib12","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1200\/JCO.19.00640","article-title":"MARS: mutation-adjusted risk score for advanced systemic mastocytosis","volume":"37","author":"Jawhar","year":"2019","journal-title":"J\u00a0Clin Oncol"},{"issue":"3","key":"2022101315372740800_bib13","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1016\/S2352-3026(20)30400-2","article-title":"Proposed global prognostic score for systemic mastocytosis: a retrospective prognostic modelling study","volume":"8","author":"Mu\u00f1oz-Gonz\u00e1lez","year":"2021","journal-title":"Lancet Haematol"},{"issue":"8","key":"2022101315372740800_bib14","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1182\/blood-2012-07-442400","article-title":"Mast cell leukemia","volume":"121","author":"Georgin-Lavialle","year":"2013","journal-title":"Blood"},{"issue":"6","key":"2022101315372740800_bib15","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.3324\/haematol.2017.163964","article-title":"The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm","volume":"102","author":"Jawhar","year":"2017","journal-title":"Haematologica"},{"key":"2022101315372740800_bib16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.leukres.2017.05.018","article-title":"Mast cell leukemia (MCL): clinico-pathologic and molecular features and survival outcome","volume":"59","author":"Jain","year":"2017","journal-title":"Leuk Res"},{"issue":"6","key":"2022101315372740800_bib17","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/leu.2015.24","article-title":"KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis","volume":"29","author":"Arock","year":"2015","journal-title":"Leukemia"},{"issue":"5","key":"2022101315372740800_bib18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/ajh.23672","article-title":"Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis","volume":"89","author":"Kristensen","year":"2014","journal-title":"Am J Hematol"},{"issue":"12","key":"2022101315372740800_bib19","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.6004\/jnccn.2018.0088","article-title":"Systemic mastocytosis, version 2.2019, NCCN clinical practice guidelines in oncology","volume":"16","author":"Gotlib","year":"2018","journal-title":"J\u00a0Natl Compr Canc Netw"},{"issue":"3","key":"2022101315372740800_bib20","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1373\/clinchem.2017.277897","article-title":"Digital PCR: a sensitive and precise method for KIT D816V quantification in mastocytosis","volume":"64","author":"Greiner","year":"2018","journal-title":"Clin Chem"},{"issue":"14","key":"2022101315372740800_bib21","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1182\/blood-2013-04-496448","article-title":"Comprehensive mutational profiling in advanced systemic mastocytosis","volume":"122","author":"Schwaab","year":"2013","journal-title":"Blood"},{"issue":"1","key":"2022101315372740800_bib22","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/leu.2015.284","article-title":"Additional mutations in SRSF2, ASXL1 and\/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis","volume":"30","author":"Jawhar","year":"2016","journal-title":"Leukemia"},{"issue":"12","key":"2022101315372740800_bib23","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1038\/leu.2016.190","article-title":"Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2\/ASXL1\/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis","volume":"30","author":"Jawhar","year":"2016","journal-title":"Leukemia"},{"issue":"7","key":"2022101315372740800_bib24","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1182\/blood-2006-04-015545","article-title":"KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients","volume":"108","author":"Garcia-Montero","year":"2006","journal-title":"Blood"},{"issue":"5","key":"2022101315372740800_bib25","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/leu.2015.4","article-title":"Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D816V as a distinct and late event","volume":"29","author":"Jawhar","year":"2015","journal-title":"Leukemia"},{"issue":"4","key":"2022101315372740800_bib26","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1136\/mp.53.4.188","article-title":"Detection of c-kit mutation Asp 816 to Val in microdissected bone marrow infiltrates in a case of systemic mastocytosis associated with chronic myelomonocytic leukaemia","volume":"53","author":"Sotlar","year":"2000","journal-title":"Mol Pathol"},{"issue":"5","key":"2022101315372740800_bib27","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/path.2677","article-title":"Variable presence of KITD816V in clonal haematological non-mast cell lineage diseases associated with systemic mastocytosis (SM-AHNMD)","volume":"220","author":"Sotlar","year":"2010","journal-title":"J\u00a0Pathol"},{"issue":"2","key":"2022101315372740800_bib28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1182\/blood-2017-01-764423","article-title":"Response and progression on midostaurin in advanced systemic mastocytosis: KIT D816V and other molecular markers","volume":"130","author":"Jawhar","year":"2017","journal-title":"Blood"},{"issue":"2","key":"2022101315372740800_bib29","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/leu.2017.234","article-title":"Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis: 10-year median follow-up of a phase II trial","volume":"32","author":"DeAngelo","year":"2018","journal-title":"Leukemia"},{"issue":"26","key":"2022101315372740800_bib30","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1056\/NEJMoa1513098","article-title":"Efficacy and safety of midostaurin in advanced systemic mastocytosis","volume":"374","author":"Gotlib","year":"2016","journal-title":"N\u00a0Engl J Med"},{"issue":"7","key":"2022101315372740800_bib31","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0145-2126(02)00168-6","article-title":"Aggressive systemic mastocytosis and related mast cell disorders: current treatment options and proposed response criteria","volume":"27","author":"Valent","year":"2003","journal-title":"Leuk Res"},{"issue":"2","key":"2022101315372740800_bib32","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1182\/blood-2005-10-4149","article-title":"Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia","volume":"108","author":"Cheson","year":"2006","journal-title":"Blood"},{"issue":"13","key":"2022101315372740800_bib33","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1182\/blood-2012-09-458521","article-title":"International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis","volume":"121","author":"Gotlib","year":"2013","journal-title":"Blood"},{"key":"2022101315372740800_bib34","unstructured":"Center for Drug Evaluation and Research\n          . Medical review. avapritinib. Accessed 19 June 2022. Available at:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2017\/207997Orig1Orig2s000MedR.pdf."},{"key":"2022101315372740800_bib35","unstructured":"European Medicines Agency\n          . Summary of Product Characteristics: Midostaurin. Accessed 19 June 2022. Available at:https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/rydapt."},{"issue":"414","key":"2022101315372740800_bib36","doi-asserted-by":"crossref","first-page":"eaao1690","DOI":"10.1126\/scitranslmed.aao1690","article-title":"A\u00a0precision therapy against cancers driven by KIT\/PDGFRA mutations","volume":"9","author":"Evans","year":"2017","journal-title":"Sci Transl Med"},{"issue":"12","key":"2022101315372740800_bib37","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1038\/s41591-021-01538-9","article-title":"Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial","volume":"27","author":"DeAngelo","year":"2021","journal-title":"Nat Med"},{"issue":"suppl 1","key":"2022101315372740800_bib38","article-title":"Efficacy of avapritinib in patients with advanced systemic mastocytosis: hematologic and bone marrow responses from the phase 2 open-label, single-arm, pathfinder study","volume":"138","author":"George","year":"2021","journal-title":"Blood"},{"issue":"suppl 1","key":"2022101315372740800_bib39","article-title":"Effective control of advanced systemic mastocytosis with avapritinib: mutational analysis from the EXPLORER clinical study","volume":"138","author":"Deininger","year":"2021","journal-title":"Blood"},{"issue":"12","key":"2022101315372740800_bib40","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1038\/s41591-021-01539-8","article-title":"Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial","volume":"27","author":"Gotlib","year":"2021","journal-title":"Nat Med"},{"issue":"suppl 1","key":"2022101315372740800_bib41","doi-asserted-by":"crossref","first-page":"S367","DOI":"10.1016\/S2152-2650(21)01843-7","article-title":"Efficacy and safety of \u2264200 mg avapritinib in patients with advanced systemic mastocytosis: pooled results from the phase 1 EXPLORER and phase 2 PATHFINDER studies","volume":"21","author":"Radia","year":"2021","journal-title":"Clin Lymphoma Myeloma Leukemia"},{"key":"2022101315372740800_bib42","doi-asserted-by":"crossref","DOI":"10.1182\/bloodadvances.2022007539","article-title":"Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis","author":"Reiter","year":"2022","journal-title":"Blood Adv"},{"issue":"22","key":"2022101315372740800_bib43","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.3390\/ijms22062983","article-title":"Response criteria in advanced systemic mastocytosis: evolution in the era of KIT inhibitors","volume":"15","author":"Shomali","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2022101315372740800_bib44","unstructured":"Food and Drug Administration\n          . Medical review. Avapritinib: highlights of prescribing information. Accessed 19 June 2022. Available at:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/212608s007lbl.pdf."},{"key":"2022101315372740800_bib45","unstructured":"European Medicines Agency\n          . Summary of Product Characteristics: Ayvakyt. Accessed 19 June 2022. Available at:https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/ayvakyt-epar-product-information_en.pdf."},{"issue":"8","key":"2022101315372740800_bib46","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1038\/s41375-022-01615-z","article-title":"Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis","volume":"36","author":"Reiter","year":"2022","journal-title":"Leukemia"},{"issue":"13","key":"2022101315372740800_bib47","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.2217\/fon-2021-1509","article-title":"Indirect treatment comparisons of avapritinib versus midostaurin for patients with advanced systemic mastocytosis","volume":"18","author":"Pilkington","year":"2022","journal-title":"Future Oncol"},{"issue":"1","key":"2022101315372740800_bib48","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jaip.2018.09.024","article-title":"The data registry of the European Competence Network on Masotcytosis (ECNM): set up, projects, and perspectives","volume":"7","author":"Valent","year":"2019","journal-title":"J\u00a0Allergy Clin Immunol Pract"},{"issue":"suppl","key":"2022101315372740800_bib49","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1097\/01.HS9.0000846936.51452.f2","article-title":"HARBOR, a phase 2\/3 study of BLU-263 in patients with indolent systemic mastocytosis and monoclonal mast cell activation syndrome","volume":"6","author":"Castells","year":"2022","journal-title":"Hemasphere"},{"issue":"29","key":"2022101315372740800_bib50","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1200\/JCO.2014.55.2018","article-title":"Hematopoietic stem-cell transplantation for advanced systemic mastocytosis","volume":"32","author":"Ustun","year":"2014","journal-title":"J\u00a0Clin Oncol"},{"key":"2022101315372740800_bib51","first-page":"1","article-title":"Rapid response to avapritinib of acute myeloid leukemia with t(8;21) and KIT mutation relapse post allo-HSCT","volume":"19","author":"Xue","year":"2022","journal-title":"Leuk Lymphoma"},{"key":"2022101315372740800_bib52","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ebiom.2019.03.089","article-title":"Single-cell analysis reveals the KIT D816V mutation in haematopoietic stem and progenitor cells in systemic mastocytosis","volume":"43","author":"Grootens","year":"2019","journal-title":"EBioMedicine"},{"issue":"suppl 1","key":"2022101315372740800_bib53","article-title":"A\u00a0phase 2 study of bezuclastinib (CGT9486), an oral, selective, and potent KIT D816V inhibitor, in adult patients with advanced systemic mastocytosis","volume":"138","author":"Gotlib","year":"2021","journal-title":"Blood"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/140\/15\/1667\/1924894\/blood_bld-2021-014612-c-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/140\/15\/1667\/1924894\/blood_bld-2021-014612-c-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T11:38:38Z","timestamp":1665661118000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/140\/15\/1667\/486003\/Avapritinib-for-advanced-systemic-mastocytosis"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,13]]},"references-count":53,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2022,10,13]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2021014612","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,13]]}}}