{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:40:25Z","timestamp":1792215625704,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Melanoma is an aggressive type of skin cancer. Immune checkpoint inhibitors (ICIs): pembrolizumab, ipilimumab and\/or nivolumab are recommended for the treatment of metastatic melanoma. ICIs enhance the immune response by blocking PD\u20101 and\/or CTLA\u20104, improving remission and overall survival (OS). However, ICIs can cause immune\u2010related adverse events (irAEs) such as colitis and dermatitis. Recent studies have demonstrated association between irAEs and improved tumour regression. This study aimed to evaluate the relationship between OS and stopping ICIs therapy due to immunological toxicity in metastatic melanoma patients. This study was approved by The University Hospitals Sussex NHS Foundation Trust (UHSussex) (reference 1963) and the University of Brighton (reference 2024\u201312,878\u2010Shamsaldeen). Data collected from files of patients diagnosed with metastatic melanoma treated with ICIs at UHSussex between October 2011 to December 2022. In a total of 344 metastatic melanoma patients, the OS was 41.3%. There were 184 patients (53.5%) experienced irAEs. Among 202 patients who died by the cut\u2010off point, there were 115 (56.9%) patients who did not experience irAE, while 68.3% of the 142 patients who were alive experienced irAE revealing overall association (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001, Pearson's\n                    <jats:italic>R<\/jats:italic>\n                    \u2009=\u20090.249) with logistics regression analysis showed association between irAE and OS (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Kaplan\u2013Meier survival analysis showed significant longer OS (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) for patients experienced irAE. Stopping ICIs due to toxicity reported in 83 patients from which 56 patients were alive by the cut\u2010off point (67.5%) revealing overall association (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001, Pearson's\n                    <jats:italic>R<\/jats:italic>\n                    \u2009=\u20090.171) with logistics regression analysis showed association between stopping ICI due to toxicity and OS (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Kaplan\u2013Meier survival analysis showed significant longer OS (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.027) in patients whom their ICI therapy was stopped due to immune\u2010related toxicity. In conclusion, the positive correlation between irAEs and survival may highlight the potential value of irAEs and irAE\u2010related toxicity as biomarkers for therapeutic efficacy in advanced melanoma management.\n                  <\/jats:p>","DOI":"10.1002\/cam4.72119","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T07:34:34Z","timestamp":1784705674000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune\u2010Related Adverse Events and Therapeutic Outcomes After Stopping Immune Checkpoint Inhibitors due to Toxicity Among Patients With Metastatic Melanoma (University Hospitals Sussex)"],"prefix":"10.1002","volume":"15","author":[{"given":"Karmen","family":"Iessa","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Applied Sciences University of Brighton  Moulsecoomb, Brighton East Sussex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6623-9995","authenticated-orcid":false,"given":"Kavita","family":"Kantilal","sequence":"additional","affiliation":[{"name":"University Hospitals Sussex, Royal Sussex County Hospital  Brighton East Sussex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ieda","family":"Garekyaragh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Applied Sciences University of Brighton  Moulsecoomb, Brighton East Sussex UK"},{"name":"University Hospitals Sussex, Royal Sussex County Hospital  Brighton East Sussex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Paget","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Applied Sciences University of Brighton  Moulsecoomb, Brighton East Sussex UK"},{"name":"University Hospitals Sussex, Royal Sussex County Hospital  Brighton East Sussex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Mangan","sequence":"additional","affiliation":[{"name":"University Hospitals Sussex, Royal Sussex County Hospital  Brighton East Sussex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8203-0067","authenticated-orcid":false,"given":"Yousif A.","family":"Shamsaldeen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Applied Sciences University of Brighton  Moulsecoomb, Brighton East Sussex UK"},{"name":"Department of Pharmacy and Biomolecular Sciences, The Faculty of Health, Innovation, Technology and Science (HITS) Liverpool John Moores University  Liverpool Merseyside UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"The National Institute for Health and Care Excellence \u201cMelanoma: Assessment and Manangement \u201d2022 https:\/\/www.nice.org.uk\/guidance\/ng14\/chapter\/Recommendations#managing\u2010stages\u20100\u2010to\u2010ii\u2010melanoma."},{"key":"e_1_2_11_3_1","unstructured":"Melanoma UK \u201cStatistics \u201d2022 https:\/\/www.melanomauk.org.uk\/statistics."},{"key":"e_1_2_11_4_1","unstructured":"Cancer Research UK \u201cMelanoma Skin Cancer Statistics \u201d2025 https:\/\/www.cancerresearchuk.org\/health\u2010professional\/cancer\u2010statistics\/statistics\u2010by\u2010cancer\u2010type\/melanoma\u2010skin\u2010cancer#heading\u2010Zero."},{"key":"e_1_2_11_5_1","unstructured":"National Institute for Health and Care Excellence \u201cNivolumab\u2013Relatlimab for Untreated Unresectable or Metastatic Melanoma in People 12\u2009Years and Over \u201d2024 https:\/\/www.nice.org.uk\/guidance\/ta950."},{"key":"e_1_2_11_6_1","volume-title":"StatPearls [Internet]","author":"Saad P.","year":"2023"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2016.1199310"},{"key":"e_1_2_11_8_1","volume-title":"StatPearls [Internet]","author":"Rendon A.","year":"2024"},{"key":"e_1_2_11_9_1","volume-title":"CheckMate 067: 6.5\u2010Year Outcomes in Patients (pts) With Advanced Melanoma","author":"Wolchok J. 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