{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:02:17Z","timestamp":1784872937772,"version":"3.55.0"},"reference-count":14,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"unspecified","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Blitzer Family Fund","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,8,6]]},"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The combination of ipilimumab and nivolumab is a highly effective treatment for metastatic cutaneous melanoma. However, immune-related adverse events (irAEs) are common, often necessitating treatment interruption and the use of immunosuppressive agents. There is no data on the impact of resuming nivolumab on survival following recovery from the irAE and completion of immunosuppressive treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and methods<\/jats:title>\n                  <jats:p>In this retrospective analysis, we examined a cohort of patients treated with ipilimumab\/nivolumab who developed irAEs requiring treatment interruption and immunosuppressive therapy. The differences in physician practice patterns at our institution allowed us to examine the survival effect of restarting single-agent nivolumab. A multivariate analysis of clinical factors associated with improved survival was performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 165 patients who were treated with ipilimumab\/nivolumab and developed irAEs requiring treatment interruption and immunosuppressive therapy. Patients with the best overall response of progressive disease were excluded. Of the remaining 122 patients, 46 resumed single-agent nivolumab. When stratified by age and adjusted for sex, M-stage, lactate dehydrogenase (LDH), therapy duration, and irAE type, the effect of resumption of nivolumab on survival was highly significant (p=0.02). Patients who resumed nivolumab had a 68% reduction in the hazard of death compared with patients who had not yet or never resumed nivolumab (HR: 0.32, 95%\u2009CI: 0.12 to 0.84). Of the patients who resumed nivolumab, 12 (26%) patients had subsequent irAEs, with five patients having grade 3 irAEs. No grade 4 or 5 irAEs were noted.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Resuming single-agent nivolumab following a treatment interruption for ipilimumab\/nivolumab-associated irAE and completion of immunosuppressive therapy increased overall survival compared with discontinuing nivolumab permanently in patients with metastatic melanoma. Toxicity observed post-resumption of single-agent nivolumab was manageable with no severe irAEs observed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2024-009061","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:45:17Z","timestamp":1724892317000},"page":"e009061","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Nivolumab maintenance improves overall survival of patients with advanced melanoma who experience severe immune-related adverse events on nivolumab plus ipilimumab"],"prefix":"10.1136","volume":"12","author":[{"given":"Anna K","family":"Maloney","sequence":"first","affiliation":[{"name":"Quinnipiac University Frank H Netter MD School of Medicine, North Haven, Connecticut, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Giobbie-Hurder","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Katukota","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miklos C","family":"Fogarasi","sequence":"additional","affiliation":[{"name":"Quinnipiac University Frank H Netter MD School of Medicine, North Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4253-943X","authenticated-orcid":false,"given":"Patrick A","family":"Ott","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F Stephen","family":"Hodi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3429-4468","authenticated-orcid":false,"given":"Tamara A","family":"Sussman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3877-3984","authenticated-orcid":false,"given":"Ann W","family":"Silk","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizwan","family":"Haq","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Insco","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7979-8953","authenticated-orcid":false,"given":"Elizabeth I","family":"Buchbinder","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"2025100307441141000_12.8.e009061.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1302369"},{"key":"2025100307441141000_12.8.e009061.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"2025100307441141000_12.8.e009061.3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01763"},{"key":"2025100307441141000_12.8.e009061.4","first-page":"212","article-title":"Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial","volume":"41","author":"Ascierto","year":"2023","journal-title":"J C O"},{"key":"2025100307441141000_12.8.e009061.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109970"},{"key":"2025100307441141000_12.8.e009061.6","doi-asserted-by":"crossref","DOI":"10.1186\/s40425-017-0300-z","article-title":"Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group","volume":"5","author":"Puzanov","year":"2017","journal-title":"J Immunother Cancer"},{"key":"2025100307441141000_12.8.e009061.7","doi-asserted-by":"crossref","DOI":"10.1186\/s40425-019-0779-6","article-title":"Incidence rates of immune-related adverse events and their correlation with response in advanced solid tumours treated with NIVO or NIVO+IPI: a systematic review and meta-analysis","volume":"7","author":"Xing","year":"2019","journal-title":"J Immunother Cancer"},{"key":"2025100307441141000_12.8.e009061.8","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1136"},{"key":"2025100307441141000_12.8.e009061.9","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1001\/jamaoncol.2017.2391","article-title":"Measuring Toxic Effects and Time to Treatment Failure for Nivolumab Plus Ipilimumab in Melanoma","volume":"4","author":"Shoushtari","year":"2018","journal-title":"JAMA Oncol"},{"key":"2025100307441141000_12.8.e009061.10","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1200\/JCO.21.01570","article-title":"Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study)","volume":"40","author":"Postow","year":"2022","journal-title":"J Clin Oncol"},{"key":"2025100307441141000_12.8.e009061.11","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/bjd.20879","article-title":"Early tumour response assessment may avoid serious immune-related adverse events in nivolumab and ipilimumab combination therapy for stage IV melanoma","volume":"186","author":"Maeda","year":"2022","journal-title":"Br J Dermatol"},{"key":"2025100307441141000_12.8.e009061.12","doi-asserted-by":"crossref","DOI":"10.1186\/s12885-024-12336-0","article-title":"Safe Stop IPI-NIVO trial: early discontinuation of nivolumab upon achieving a complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab - study protocol","volume":"24","author":"Janssen","year":"2024","journal-title":"BMC Cancer"},{"key":"2025100307441141000_12.8.e009061.13","doi-asserted-by":"crossref","unstructured":"Blank CU , Lucas MW , Scolyer RA , et al . Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma. N Engl J Med 2024. doi:10.1056\/NEJMoa2402604","DOI":"10.1056\/NEJMoa2402604"},{"key":"2025100307441141000_12.8.e009061.14","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx642"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2024-009061","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T14:44:19Z","timestamp":1759502659000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2024-009061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":14,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,28]]},"published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1136\/jitc-2024-009061"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2024-009061","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8]]}}}