{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:03:25Z","timestamp":1792785805592,"version":"4.5.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Allakos, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Indolent systemic mastocytosis (ISM) is characterized by excessive mast cell (MC) accumulation and MC-driven signs and symptoms. Currently used therapies are not approved and have limited efficacy. Lirentelimab (AK002) is a monoclonal antibody against sialic acid-binding immunoglobulin-like lectin (Siglec)-8 that inhibits MC activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine the safety, tolerability and efficacy of lirentelimab in reducing the symptoms of ISM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>At a specialty centre for mastocytosis in Germany, we conducted a phase I first-in-human single-ascending and multidose clinical trial of lirentelimab in patients with ISM. Eligible adults had World Health Organization-confirmed ISM and an unsatisfactory response to available treatment. In part A, patients received a single dose of lirentelimab 0.0003, 0.001, 0.003, 0.01 or 0.03\u2005mg kg\u20131; in part B, patients received one lirentelimab dose of 0.3\u2005mg kg\u20131 or 1.0\u2005mg kg\u20131; and in part C, patients received either 1.0\u2005mg kg\u20131 lirentelimab every 4 weeks for 6\u2005months or ascending doses of lirentelimab (one dose of 1\u2005mg kg\u20131 followed by five doses of 3\u201310\u2005mg kg\u20131 every 4 weeks). The primary endpoint was safety\/tolerability. Secondary endpoints included changes from baseline in Mastocytosis Symptom Questionnaire (MSQ), Mastocytosis Activity Score (MAS) and Mastocytosis Quality of Life Questionnaire (MC-QoL) scores at 2 weeks after the final dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In 25 patients with ISM (13 in parts A + B and 12 in part C; median age 51\u2005years, 76% female, median 4.6\u2005years from diagnosis), the most common treatment-related adverse events (AEs) were feeling hot (76%) and experiencing a headache (48%). No serious AEs occurred. Median MSQ and MAS symptom severity scores in part C improved (vs. baseline) across all symptoms [MSQ: skin (38\u201356%), gastrointestinal (49\u201360%), neurological (47\u201359%), musculoskeletal (26\u201327%); MAS: skin (53\u201359%), gastrointestinal (72\u201385%), neurological (20\u201357%), musculoskeletal (25%)]. Median MC-QoL scores improved across all domains: symptoms (39%), social life\/functioning (42%), emotions (57%) and skin (44%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lirentelimab was generally well tolerated and improved symptoms and quality of life in patients with ISM. The therapeutic potential of lirentelimab should be considered for ISM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljad191","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T01:28:17Z","timestamp":1686187697000},"page":"511-519","source":"Crossref","is-referenced-by-count":28,"title":["Safety and efficacy of lirentelimab in patients with\u00a0refractory indolent systemic mastocytosis: a first-in-human clinical trial"],"prefix":"10.1093","volume":"189","author":[{"given":"Frank","family":"Siebenhaar","sequence":"first","affiliation":[{"name":"Institute of Allergology"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Altrichter","sequence":"additional","affiliation":[{"name":"Institute of Allergology"},{"name":"Department of Dermatology and Venerology, Kepler University 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Berlin, Berlin, Germany, and Berlin Institute of Health, Berlin, Germany)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M","family":"Kantor","sequence":"additional","affiliation":[{"name":"Allakos , San Carlos, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan T","family":"Chang","sequence":"additional","affiliation":[{"name":"Allakos , San Carlos, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford A","family":"Youngblood","sequence":"additional","affiliation":[{"name":"Allakos , San Carlos, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhupinder","family":"Singh","sequence":"additional","affiliation":[{"name":"Allakos , San Carlos, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik S","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Allakos , San Carlos, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Maurer","sequence":"additional","affiliation":[{"name":"Institute of Allergology"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"2024090209452189000_ljad191-B1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/ajh.25371","article-title":"Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management","volume":"94","author":"Pardanani","year":"2019","journal-title":"Am J Hematol"},{"key":"2024090209452189000_ljad191-B2","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1182\/blood-2016-09-731893","article-title":"Mastocytosis: 2016 updated WHO classification and novel emerging treatment 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