{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:19:13Z","timestamp":1791893953934,"version":"4.3.4"},"reference-count":53,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2022,6,1]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p>On the basis of data from the German Registry on Disorders of Eosinophils and Mast Cells, we compared the efficacy of midostaurin and cladribine in patients with advanced systemic mastocytosis (AdvSM).<\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p>Patients with AdvSM (n = 139) were treated with midostaurin only (n = 63, 45%), cladribine only (n = 23, 17%), or sequentially (midostaurin-cladribine, n = 30, 57%; cladribine-midostaurin, n = 23, 43%). Prognosis was assessed through the Mutation-Adjusted Risk Score (MARS). Besides the comparison of efficacy between midostaurin and cladribine on response (eg, organ dysfunction, bone marrow mast cell [MC] infiltration, and tryptase), overall survival (OS), and leukemia-free survival, we focused on the impact of treatment on involved non-MC lineages, for example, monocytes or eosinophils, and the KIT D816V expressed allele burden.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Midostaurin only was superior to cladribine only with effects from responses on MC and non-MC lineages conferring on a significantly improved OS (median 4.2 v 1.9 years, P = .033) and leukemia-free survival (2.7 v 1.3 years, P = .044) on the basis of a propensity score\u2013weighted analysis of parameters included in MARS. Midostaurin compensated the inferior efficacy of cladribine in first- and second-line treatment. On midostaurin in any line, response of eosinophilia did not improve its baseline adverse prognostic impact, whereas response of monocytosis proved to be a positive on-treatment parameter. Multivariable analysis allowed to establish three risk categories (low\/intermediate\/high) through the combination of MARS and the reduction of the KIT D816V expressed allele burden of \u2265 25% at month 6 (median OS not reached v 3.0 years v 1.0 year; P &lt; .001).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>In this registry-based analysis, midostaurin revealed superior efficacy over cladribine in patients with AdvSM. In midostaurin-treated patients, the combination of baseline MARS and molecular response provided a compelling three-tier risk categorization (MARSv2.0) for OS.<\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.21.01849","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T20:59:16Z","timestamp":1646254756000},"page":"1783-1794","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":40,"title":["Superior Efficacy of Midostaurin Over Cladribine in Advanced Systemic Mastocytosis: A Registry-Based Analysis"],"prefix":"10.1200","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-1504","authenticated-orcid":false,"given":"Johannes","family":"L\u00fcbke","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, 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