{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:36:09Z","timestamp":1790073369841,"version":"4.0.1"},"reference-count":29,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T00:00:00Z","timestamp":1581638400000},"content-version":"unspecified","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2019,12,15]]},"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors (ICI) induce a range of immune-related adverse events (irAEs) with various degrees of severity. While clinical experience with ICI retreatment following clinically significant irAEs is growing, the safety and efficacy are not yet well characterized.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This multicenter retrospective study identified patients with metastatic renal cell carcinoma treated with ICI who had &gt;1\u2009week therapy interruption for irAEs. Patients were classified into retreatment and discontinuation cohorts based on whether or not they resumed an ICI. Toxicity and clinical outcomes were assessed descriptively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 499 patients treated with ICIs, 80 developed irAEs warranting treatment interruption; 36 (45%) of whom were restarted on an ICI and 44 (55%) who permanently discontinued. Median time to initial irAE was similar between the retreatment and discontinuation cohorts (2.8 vs 2.7 months, p=0.59). The type and grade of irAEs were balanced across the cohorts; however, fewer retreatment patients required corticosteroids (55.6% vs 84.1%, p=0.007) and hospitalizations (33.3% vs 65.9%, p=0.007) for irAE management compared with discontinuation patients. Median treatment holiday before reinitiation was 0.9 months (0.2\u201331.6). After retreatment, 50% (n=18\/36) experienced subsequent irAEs (12 new, 6 recurrent) with 7 (19%) grade 3 events and 13 drug interruptions. Median time to irAE recurrence after retreatment was 2.8 months (range: 0.3\u201313.8). Retreatment resulted in 6 (23.1%) additional responses in 26 patients whose disease had not previously responded. From first ICI initiation, median time to next therapy was 14.2 months (95%\u2009CI 8.2 to 18.9) and 9.0 months (5.3 to 25.8), and 2-year overall survival was 76% (95%CI 55% to 88%) and 66% (48% to 79%) in the retreatment and discontinuation groups, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Despite a considerable rate of irAE recurrence with retreatment after a prior clinically significant irAE, most irAEs were low grade and controllable. Prospective studies are warranted to confirm that retreatment enhances survival outcomes that justify the safety risks.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2019-000144","type":"journal-article","created":{"date-parts":[[2020,2,17]],"date-time":"2020-02-17T03:59:30Z","timestamp":1581911970000},"page":"e000144","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":72,"title":["Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma"],"prefix":"10.1136","volume":"8","author":[{"given":"Sarah","family":"Abou Alaiwi","sequence":"first","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanling","family":"Xie","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"Flippot","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Department of Medical Oncology, Gustave Roussy Institute, Villejuif, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nieves","family":"Martinez-Chanza","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Department of Medical Oncology, Institut Jules Bordet, Bruxelles, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley A","family":"McGregor","sequence":"additional","affiliation":[{"name":"Medical 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