{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:36:23Z","timestamp":1770899783823,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013170","name":"Ono Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although malignant melanoma is relatively rare in Japan, it is often diagnosed at a later stage than in Western countries. Nivolumab and ipilimumab are immune checkpoint inhibitors targeting programmed death 1 and cytotoxic T\u2010lymphocyte\u2010associated protein 4, respectively. Owing to their complementary anticancer effects, nivolumab and ipilimumab combination therapy (N\u2009+\u2009I) has been studied and approved for treating malignant melanoma in various countries including Japan. Real\u2010world postmarketing surveillance was implemented to record treatment\u2010related adverse events (TRAEs) in patients treated with N\u2009+\u2009I following its approval in Japan. Patients were eligible for registration if they had unresectable malignant melanoma and started N\u2009+\u2009I between September 2018 and August 2019. The observation period was 13\u2009weeks from starting N\u2009+\u2009I. Only safety information was collected and evaluated. The final case report form lock was March 2021. Overall, 173 patients (median age, 66.0\u2009years; performance status 0\u20131, 88.4%; skin: 53.2%; mucosal: 32.4%) were eligible for the analyses. Overall, 34.1% of patients completed 4 doses of N\u2009+\u2009I. N\u2009+\u2009I was discontinued by 63.0% (due to adverse events in 67.9% and disease progression\/death in 22.9%). Any grade and grade\u2009\u22653 TRAEs were reported in 73.41% and 52.02%, respectively. TRAEs in \u226510 patients were hepatic function abnormal (any grade\/grade\u2009\u22653: 23.12%\/13.29%), pyrexia (10.40%\/0.58%), diarrhea (9.25%\/2.89%), rash (8.67%\/0.58%), hypophysitis (5.78%\/5.20%), interstitial lung disease (5.78%\/2.89%), and liver disorder (5.78%\/4.62%). TRAEs were classified as recovered (36.99% of patients), recovering (44.51%), unrecovered (13.29%), recovered with sequelae (2.31%), and death (1.73%). Overall, 24 of 34 patients (70.59%) with gastrointestinal\u2010related and 53 of 65 (81.54%) liver\u2010related TRAEs received treatment, such as a steroid with\/without an immunosuppressant; most patients recovered within 1 to 2\u2009months. In conclusion, this postmarketing surveillance of N\u2009+\u2009I in patients with unresectable malignant melanoma revealed no new safety concerns compared with results of prior studies. Immune\u2010related TRAEs were generally manageable by appropriate treatment including a steroid.<\/jats:p>","DOI":"10.1111\/1346-8138.16820","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T23:07:07Z","timestamp":1687648027000},"page":"1108-1120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Postmarketing surveillance of nivolumab plus ipilimumab combination therapy in Japanese patients with unresectable malignant melanoma"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9638-0428","authenticated-orcid":false,"given":"Naoya","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Department of Dermatologic Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshio","family":"Kiyohara","sequence":"additional","affiliation":[{"name":"Dermatology Division Shizuoka Cancer Center Hospital  Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5391-3397","authenticated-orcid":false,"given":"Hisashi","family":"Uhara","sequence":"additional","affiliation":[{"name":"Department of Dermatology Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6847-8682","authenticated-orcid":false,"given":"Tetsuya","family":"Tsuchida","sequence":"additional","affiliation":[{"name":"Department of Dermatology Saitama Medical University  Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Patient Safety Japan, Bristol\u2010Myers Squibb K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Yamada","sequence":"additional","affiliation":[{"name":"Patient Safety Japan, Bristol\u2010Myers Squibb K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Komoto","sequence":"additional","affiliation":[{"name":"Patient Safety Japan, Bristol\u2010Myers Squibb K.K.  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Chapter 4. Post\u2010marketing surveillance of drugs [cited April 13 2023]. 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