{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T09:54:58Z","timestamp":1781862898724,"version":"3.54.5"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Immune checkpoint inhibitors have significantly improved survival in metastatic melanoma. Combination nivolumab plus ipilimumab demonstrated superior efficacy in randomized trials, including CheckMate 067, but data beyond the first-line setting remain limited. This study evaluated real-world outcomes and predictors of response across different lines of therapy, with an exploratory comparison between first- and second-line use. Methods: This retrospective single-center study included patients with metastatic melanoma treated with nivolumab plus ipilimumab as first- or second-line therapy at Moscow City Oncology Hospital No. 62 between September 2015 and October 2023. Eligible patients had histologically confirmed melanoma and received at least one cycle of dual immune checkpoint blockade. Clinical and demographic data were extracted from electronic medical records. The primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included objective response rate (ORR) and safety. Survival outcomes were estimated using the Kaplan\u2013Meier method and compared using the log-rank test. Multivariable Cox proportional hazards models adjusted for clinically relevant covariates were applied to evaluate the association between treatment line and survival outcomes. Additional prognostic analyses were performed using backward stepwise multivariable Cox regression. Results: Median follow-up was 18.2 months (IQR, 6.7\u201330.4). Median PFS in the overall cohort was 7.9 months (95% CI, 4.2\u201311.5), and median OS was not reached (NR); 5-year OS: 50%. The ORR was 45.8%, including 15.1% complete responses. Median PFS was 9.0 months (95% CI, 5.0\u201312.9) in first-line and 6.1 months (95% CI, 3.4\u20138.8) in second-line patients. Median OS was NR in the first-line cohort and was 30.5 months (95% CI: NR) in the second-line cohort. In exploratory analyses, OS did not differ significantly between patients treated in the first-line (n = 141) versus second-line setting (n = 63) (p = 0.848). After adjustment for clinical and demographic characteristics, line of therapy was not associated with OS (HR 0.93; 95% CI, 0.58\u20131.50; p = 0.762). Immune-related adverse events were associated with longer PFS (HR 0.66; 95% CI, 0.46\u20130.93), although this may reflect time-dependent bias. Conclusions: Nivolumab plus ipilimumab demonstrated clinically meaningful activity in both first- and second-line settings. Outcomes were numerically lower than in clinical trials, consistent with broader real-world populations. In exploratory analyses, OS did not differ significantly between treatment lines after adjustment for clinical and demographic characteristics. These findings should be interpreted with caution given the retrospective design and potential sources of bias.<\/jats:p>","DOI":"10.3390\/cancers18121994","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T09:18:43Z","timestamp":1781860723000},"page":"1994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Outcomes of Nivolumab Plus Ipilimumab in Metastatic Melanoma: A Stratified Analysis of First- and Second-Line Treatment"],"prefix":"10.3390","volume":"18","author":[{"given":"Alexandr","family":"Iurchenkov","sequence":"first","affiliation":[{"name":"Moscow City Oncology Hospital No. 62, 143423 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9366-1577","authenticated-orcid":false,"given":"Anastasia","family":"Danilova","sequence":"additional","affiliation":[{"name":"Moscow City Oncology Hospital No. 62, 143423 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1482-4604","authenticated-orcid":false,"given":"Polina","family":"Shilo","sequence":"additional","affiliation":[{"name":"Lahta Clinic, 197229 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1032-3818","authenticated-orcid":false,"given":"Vladimir","family":"Stoliarov","sequence":"additional","affiliation":[{"name":"Ledin Clinic, 121609 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Rakhmanova","sequence":"additional","affiliation":[{"name":"Moscow City Oncology Hospital No. 62, 143423 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilia","family":"Kanner","sequence":"additional","affiliation":[{"name":"Moscow City Oncology Hospital No. 62, 143423 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4739-7733","authenticated-orcid":false,"given":"Anna","family":"Basharina","sequence":"additional","affiliation":[{"name":"Pfizer Innovation LLC, 123112 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1973-1092","authenticated-orcid":false,"given":"Daniil","family":"Stroyakovskiy","sequence":"additional","affiliation":[{"name":"Moscow City Oncology Hospital No. 62, 143423 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N. 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