{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:23:24Z","timestamp":1789017804458,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T00:00:00Z","timestamp":1487635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Simtuzumab, a monoclonal antibody inhibitor of extracellular matrix enzyme lysyl oxidase\u2010like\u20102, showed preclinical promise and was well tolerated in clinical studies. A phase 2, open\u2010label study of simtuzumab was conducted in patients with primary myelofibrosis (<jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>), post\u2010polycythaemia vera <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content> and post\u2010essential thrombocythaemia <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>. Fifty\u2010four patients were randomized to receive simtuzumab alone (200 or 700\u00a0mg [<jats:italic>n<\/jats:italic>\u00a0=\u00a012 each group]) or simtuzumab (200 or 700\u00a0mg) with ruxolitinib (<jats:italic>n<\/jats:italic>\u00a0=\u00a015 each group) for 24\u00a0weeks. Simtuzumab alone or in combination with ruxolitinib showed no clinical benefit at 24\u00a0weeks. The mean serum simtuzumab trough concentrations appeared to increase dose\u2010proportionally between the 200\u2010mg and 700\u2010mg treatment groups. Therapy\u2010related serious adverse events were pyrexia, pain in extremity (both in 1 patient) and infusion reaction (in another patient). Bone marrow fibrosis (<jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>) score was reduced at 24\u00a0weeks in 2 patients (16\u00b77%) in the simtuzumab 700\u2010mg group, 1 (6\u00b77%) in the simtuzumab 200\u2010mg\u00a0+\u00a0ruxolitinib group, and 2 (13\u00b73%) in the simtuzumab 700\u2010mg + ruxolitinib group; similar numbers of patients had increased <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>. Simtuzumab alone or with ruxolitinib was well tolerated but did not produce clinical benefit nor consistently reduce <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content> in patients with <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content> by 24\u00a0weeks.<\/jats:p>","DOI":"10.1111\/bjh.14501","type":"journal-article","created":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T16:37:14Z","timestamp":1487695034000},"page":"939-949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["A phase 2 study of simtuzumab in patients with primary, post\u2010polycythaemia vera or post\u2010essential thrombocythaemia myelofibrosis"],"prefix":"10.1111","volume":"176","author":[{"given":"Srdan","family":"Verstovsek","sequence":"first","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Savona","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben A.","family":"Mesa","sequence":"additional","affiliation":[{"name":"Mayo Clinic Scottsdale AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Dong","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. 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