{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:39:27Z","timestamp":1787647167278,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T00:00:00Z","timestamp":1570060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["NCI K23 CA204726"],"award-info":[{"award-number":["NCI K23 CA204726"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","award":["R01CA227481"],"award-info":[{"award-number":["R01CA227481"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002224","name":"Melanoma Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002224","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,1,15]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Anti\u2013programmed death protein 1 (anti\u2013PD\u20101) agents have transformed the treatment of advanced melanoma and other cancers, but the rates of steroid\u2010refractory toxicities and health care utilization are not well described. This study assessed these endpoints in patients with melanoma treated with anti\u2013PD\u20101 with or without ipilimumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study retrospectively evaluated 344 patients with metastatic melanoma treated with anti\u2013PD\u20101 or a combination of ipilimumab and nivolumab at Vanderbilt University Medical Center from 2009 to 2018. The incidence, types, grades, management, and outcomes of immune\u2010related adverse events (irAEs) and hospitalizations for irAEs and disease progression were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients on combination therapy were more likely to develop irAEs than those on monotherapy (72% vs 37%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) and were more likely to require systemic steroids (61% vs 20%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), steroid dose re\u2010escalation (23% vs 6%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), and second\u2010line immunosuppressive use (17% vs 2%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) and to suffer high\u2010dose steroid\u2013refractory toxicities (23% vs 3%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001). Combination\u2010treated patients were more likely to have any hospitalization (32% vs 7%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) or multiple hospitalizations for irAEs (11% vs 3%; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.001) and had a longer average time of hospitalization (mean, 1.92 vs 0.62\u00a0days; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.002). Among 176 hospitalizations related to disease progression in patients who died during evaluable follow\u2010up, 69% occurred within the 90\u00a0days before death. Early hospitalizations for disease\u2010related reasons portended a very poor prognosis (median time from admission to death, 58\u00a0days).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients treated with a combination of ipilimumab and nivolumab had higher rates of hospitalization and steroid\u2010refractory toxicities than those treated with anti\u2013PD\u20101 monotherapy. Disease\u2010associated hospitalizations were similar between the 2 groups, portended a poor prognosis, and mostly occurred in the last months of life.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.32542","type":"journal-article","created":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T08:39:44Z","timestamp":1570091984000},"page":"322-328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Health care utilization and steroid\u2010refractory toxicities from immune checkpoint inhibitors"],"prefix":"10.1002","volume":"126","author":[{"given":"Laura X.","family":"Wang","sequence":"first","affiliation":[{"name":"Vanderbilt School of Medicine Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry T.","family":"Quach","sequence":"additional","affiliation":[{"name":"Vanderbilt School of Medicine Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikil V.","family":"Moodabigil","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Sosman","sequence":"additional","affiliation":[{"name":"Department of Medicine Northwestern University Medical Center and Robert H. Lurie Comprehensive Cancer Center Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacie B.","family":"Dusetzina","sequence":"additional","affiliation":[{"name":"Department of Health Policy Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6390-773X","authenticated-orcid":false,"given":"Douglas B.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412082"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00083-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003466"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709684"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.3923"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30533-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703481"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.13995"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.2391"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609214"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0210-0"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.66.1389"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31629"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-1426-2-19"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izy104"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30700-9"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-6773.2010.01082.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.4059"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30259"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.9258"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2018.7070"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30258"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805453"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.32542","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.32542","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.32542","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.32542","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T13:45:20Z","timestamp":1760276720000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.32542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,3]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,1,15]]}},"alternative-id":["10.1002\/cncr.32542"],"URL":"https:\/\/doi.org\/10.1002\/cncr.32542","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,3]]},"assertion":[{"value":"2019-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}