{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:26:30Z","timestamp":1786976790844,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,29]],"date-time":"2020-02-29T00:00:00Z","timestamp":1582934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Urelumab, a fully human, non\u2010ligand binding, CD137 agonist IgG4 monoclonal antibody, enhances T\u2010cell and natural killer\u2010cell antitumor activity in preclinical models, and may enhance cytotoxic activity of rituximab. Here we report results in patients with relapsed or refractory diffuse large B\u2010cell lymphoma (DLBCL), follicular lymphoma (FL), and other B\u2010cell lymphomas, in phase 1 studies evaluating urelumab alone (NCT01471210) or combined with rituximab (NCT01775631). Sixty patients received urelumab (0.3 mg\/kg IV Q3W, 8 mg IV Q3W, or 8 mg IV Q6W); 46 received urelumab (0.1 mg\/kg, 0.3 mg\/kg, or 8 mg IV Q3W)\u2009plus\u2009rituximab 375\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    IV QW. The maximum tolerated dose (MTD) of urelumab was determined to be 0.1 mg\/kg or 8 mg Q3W after a single event of potential drug\u2010induced liver injury occurred with urelumab 0.3 mg\/kg. Treatment\u2010related AEs were reported in 52% (urelumab: grade 3\/4, 15%) and 72% (urelumab + rituximab: grade 3\/4, 28%); three led to discontinuation (grade 3 increased AST, grade 4 acute hepatitis [urelumab]; one death from sepsis syndrome [urelumab plus rituximab]). Objective response rates\/disease control rates were 6%\/19% (DLBCL, n = 31), 12%\/35% (FL, n = 17), and 17%\/42% (other B\u2010cell lymphomas, n = 12) with urelumab and 10%\/24% (DLBCL, n = 29) and 35%\/71% (FL, n = 17) with urelumab plus rituximab. Durable remissions in heavily pretreated patients were achieved; however, many were observed at doses exceeding the MTD. These data show that urelumab alone or in combination with rituximab demonstrated manageable safety in B\u2010cell lymphoma, but the combination did not enhance clinical activity relative to rituximab alone or other current standard of care.\n                  <\/jats:p>","DOI":"10.1002\/ajh.25757","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T04:55:28Z","timestamp":1581569728000},"page":"510-520","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Urelumab alone or in combination with rituximab in patients with relapsed or refractory B\u2010cell lymphoma"],"prefix":"10.1002","volume":"95","author":[{"given":"John","family":"Timmerman","sequence":"first","affiliation":[{"name":"UCLA Medical Center  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Herbaux","sequence":"additional","affiliation":[{"name":"Centre Hospitalier R\u00e9gional Universitaire de Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Ribrag","sequence":"additional","affiliation":[{"name":"Institut Gustave Roussy  Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Zelenetz","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roch","family":"Houot","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service H\u00e9matologie Clinique  Rennes France"},{"name":"INSERM Unit\u00e9 d\u02bcInvestigation Clinique  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sattva S.","family":"Neelapu","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Logan","sequence":"additional","affiliation":[{"name":"Simon Cancer Center Indiana University  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-9013","authenticated-orcid":false,"given":"Izidore S.","family":"Lossos","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine Sylvester Comprehensive Cancer Center  Miami Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Urba","sequence":"additional","affiliation":[{"name":"Earle A. Chiles Research Institute Providence Cancer Center  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Salles","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon Universit\u00e9 de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhakrishnan","family":"Ramchandren","sequence":"additional","affiliation":[{"name":"Karmanos Cancer Institute  Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caron","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Godwin","sequence":"additional","affiliation":[{"name":"Earle A. Chiles Research Institute Providence Cancer Center  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Carpio","sequence":"additional","affiliation":[{"name":"Hospital Universitari Vall d\u02bcHebron Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanne","family":"Lathers","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Liu","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn","family":"Neely","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyendra","family":"Suryawanshi","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Koguchi","sequence":"additional","affiliation":[{"name":"Earle A. Chiles Research Institute Providence Cancer Center  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Levy","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine  Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,29]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Clinical Practice Guidelines in Oncology. B\u2010Cell Lymphomas. 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Whitehouse Station NJ: Merck Sharp & Dohme Corp;2017."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1339"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00766"},{"key":"e_1_2_7_13_1","first-page":"4055","article-title":"PD\u20101 blockade with pembrolizumab in relapsed low grade non\u2010Hodgkin lymphoma","volume":"130","author":"Ding W","year":"2017","journal-title":"Blood"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/926321"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-741041"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0263"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1272"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-1733"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2014.47.3.283"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-223958"},{"issue":"1","key":"e_1_2_7_21_1","first-page":"P267","article-title":"Assessing the potential for enhanced antibody\u2010dependent cell\u2010mediated cytotoxicity by combining the CD137 antibody urelumab with rituximab or cetuximab in patients with refractory lymphoma or select advanced solid tumors","volume":"4","author":"Segal NH","year":"2016","journal-title":"J Immunother Cancer"},{"issue":"1","key":"e_1_2_7_22_1","first-page":"O7","article-title":"Clinical safety and efficacy assessment of the CD137 agonist urelumab alone and in combination with nivolumab in patients with hematologic and solid tumor malignancies","volume":"4","author":"Massarelli E","year":"2016","journal-title":"J Immunother Cancer"},{"key":"e_1_2_7_23_1","unstructured":"Clinicaltrials.gov.https:\/\/www.clinicaltrials.gov\/. Accessed February 24 2020."},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.2403"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1296996"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1847"},{"key":"e_1_2_7_27_1","unstructured":"Rituxan (rituximab) [package insert]. South San Francisco CA: Biogen and Genentech USA Inc;2019."},{"issue":"6","key":"e_1_2_7_28_1","first-page":"1927","article-title":"Rituximab (anti\u2010CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study","volume":"92","author":"Coiffier B","year":"1998","journal-title":"Blood"},{"issue":"2","key":"e_1_2_7_29_1","first-page":"267","article-title":"A phase I study of utomilumab (PF\u201005082566), a 4\u20101BB\/CD137 agonist, in combination with rituximab in patients with CD20+ non\u2010Hodgkin\u02bcs lymphoma","volume":"35","author":"Gopal A","year":"2017","journal-title":"Hematol Oncol"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20081822"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07195-w"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10088-1"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav5989"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.25757","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.25757","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajh.25757","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.25757","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T01:34:59Z","timestamp":1693964099000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.25757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,29]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1002\/ajh.25757"],"URL":"https:\/\/doi.org\/10.1002\/ajh.25757","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,29]]},"assertion":[{"value":"2019-10-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}