{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:55:15Z","timestamp":1791204915476,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Patients with pre-existing autoimmune disease (AID) are underrepresented in trials of immune checkpoint inhibitors (ICIs). We retrospectively compared 41 patients with stage IV melanoma and pre-existing AID with 162 contemporaneous controls without AID who received ICI treatment between November 2016 and April 2023. In the AID and control cohorts, respectively, the objective response rates were 46.3% and 32.7%, and the disease control rates were 80.5% and 51.2%. Treatment interruption attributed to worsening of the baseline AID was recorded in 11\/41 patients, while 13\/41 interrupted treatment because of toxicity distinct from the baseline AID. The full cohort contributed 114 progression-free survival (PFS) events and 92 deaths. In models adjusted for age, sex, ICI regimen and M category, AID was associated with PFS (adjusted hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.24\u20130.99; p = 0.046), whereas the association with overall survival (OS) was not statistically significant (adjusted HR 0.63, 95% CI 0.29\u20131.34; p = 0.232). These findings support the feasibility of ICI therapy in carefully selected patients with clinically stable AID, while the observational design and residual confounding require cautious interpretation of comparative outcomes.<\/jats:p>","DOI":"10.3390\/ijms27198832","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:31:31Z","timestamp":1791203491000},"page":"8832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune Checkpoint Inhibitor Data in Metastatic Melanoma with Pre-Existing Autoimmune Disease: A Real World Experience"],"prefix":"10.3390","volume":"27","author":[{"given":"Maria Grazia","family":"Vitale","sequence":"first","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1081-5313","authenticated-orcid":false,"given":"Domenico","family":"Mallardo","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Francesca","family":"Sparano","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Lucia","family":"Festino","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Vito","family":"Vanella","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Claudia","family":"Trojaniello","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Margaret","family":"Ottaviano","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8788-6574","authenticated-orcid":false,"given":"Eleonora","family":"Cioli","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"},{"name":"Dermatology Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Mario","family":"Mallardo","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Bianca Arianna","family":"Facchini","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ester","family":"Simeone","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"given":"Paolo Antonio","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS-Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"},{"name":"Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus Ipilimumab in Advanced Melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S1470-2045(15)70076-8","article-title":"Nivolumab versus Chemotherapy in Patients with Advanced Melanoma Who Progressed after Anti-CTLA-4 Treatment (CheckMate 037): A randomised, controlled, open-label, phase 3 trial","volume":"16","author":"Weber","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa2407417","article-title":"Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma","volume":"392","author":"Wolchok","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.annonc.2020.03.285","article-title":"Autoimmune Diseases and Immune-Checkpoint Inhibitors for Cancer Therapy: Review of the Literature and Personalized Risk-Based Prevention Strategy","volume":"31","author":"Haanen","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1093\/annonc\/mdw443","article-title":"Anti-PD-1 Therapy in Patients with Advanced Melanoma and Preexisting Autoimmune Disorders or Major Toxicity with Ipilimumab","volume":"28","author":"Menzies","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102687","DOI":"10.1016\/j.autrev.2020.102687","article-title":"Immune Checkpoint Inhibitors Therapies in Patients with Cancer and Preexisting Autoimmune Diseases: A Meta-Analysis of Observational Studies","volume":"19","author":"Xie","year":"2020","journal-title":"Autoimmun. 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Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1200\/JCO.2017.77.0305","article-title":"Safety of Programmed Death-1 Pathway Inhibitors among Patients with Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders","volume":"36","author":"Leonardi","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/art.40397","article-title":"Brief Report: Cancer Immunotherapy in Patients with Preexisting Rheumatic Disease: The Mayo Clinic Experience","volume":"70","author":"Richter","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1007\/s00262-021-02851-5","article-title":"Preexisting Autoimmune Disease and Immune-Related Adverse Events Associated with Anti-PD-1 Cancer Immunotherapy: A National Case Series from the Canadian Research Group of Rheumatology in Immuno-Oncology","volume":"70","author":"Hoa","year":"2021","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1136\/ard-2022-222186","article-title":"Risk of irAEs in Patients with Autoimmune Diseases Treated by Immune Checkpoint Inhibitors for Stage III or IV Melanoma: Results from a Matched Case\u2013Control Study","volume":"81","author":"Dalle","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sumimoto, H., Noda, S., Koide, H., Douke, Y., Sakai, K., Nishikawa, A., Tomioka, A., Hori, M., Nakato, H., and Kimura, Y. (2024). Pre-Existing Autoimmune Disease as a Risk Factor for Immune-Related Adverse Events in Cancer Patients Receiving Immune Checkpoint Inhibitors. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0306995"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8199","DOI":"10.2147\/CMAR.S283217","article-title":"Checkpoint Inhibitors in Melanoma Patients with Underlying Autoimmune Disease","volume":"13","author":"Dietz","year":"2021","journal-title":"Cancer Manag. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e002121","DOI":"10.1136\/jitc-2020-002121","article-title":"Combination Anti-PD1 and Ipilimumab Therapy in Patients with Advanced Melanoma and Pre-Existing Autoimmune Disorders","volume":"9","author":"Brown","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1002\/art.41068","article-title":"Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Cancer and Preexisting Autoimmune Disease: A Nationwide, Multicenter Cohort Study","volume":"71","author":"Tison","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"684","DOI":"10.18632\/oncotarget.323","article-title":"New Perspectives on the Role of Vitiligo in Immune Responses to Melanoma","volume":"2","author":"Byrne","year":"2011","journal-title":"Oncotarget"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1186\/s12967-023-04607-4","article-title":"The Role of Diabetes in Metastatic Melanoma Patients Treated with Nivolumab plus Relatlimab","volume":"21","author":"Mallardo","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2247303","DOI":"10.1080\/2162402X.2023.2247303","article-title":"Melanoma Patients with Immune-Related Adverse Events after Immune Checkpoint Inhibitors Are Characterized by a Distinct Immunological Phenotype of Circulating T Cells and M-MDSCs","volume":"12","author":"Lepper","year":"2023","journal-title":"Oncoimmunology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"M\u00fcller, B., B\u00e4renwaldt, A., Herzig, P., Zippelius, A., Maul, L.V., Hess, V., K\u00f6nig, D., and L\u00e4ubli, H. (2023). Changes of Peripheral T Cell Subsets in Melanoma Patients with Immune-Related Adverse Events. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1125111"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gazzano, M., Parizot, C., Psimaras, D., Vozy, A., Baron, M., Abbar, B., Fallet, V., Litvinova, E., Canellas, A., and Birzu, C. (2022). Anti-PD-1 Immune-Related Adverse Events Are Associated with High Therapeutic Antibody Fixation on T Cells. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1082084"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1093\/rheumatology\/ker116","article-title":"Recovery of the Immune Balance between Th17 and Regulatory T Cells as a Treatment for Systemic Lupus Erythematosus","volume":"50","author":"Yang","year":"2011","journal-title":"Rheumatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.neuron.2018.01.021","article-title":"Multiple Sclerosis: Mechanisms and Immunotherapy","volume":"97","author":"Kaskow","year":"2018","journal-title":"Neuron"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1600-065X.2008.00628.x","article-title":"Th17 Cells in Human Disease","volume":"223","author":"Tesmer","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-immunol-032713-120225","article-title":"Immunology of Psoriasis","volume":"32","author":"Lowes","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1038\/s43018-023-00610-2","article-title":"Interleukin 17 Signaling Supports Clinical Benefit of Dual CTLA-4 and PD-1 Checkpoint Inhibition in Melanoma","volume":"4","author":"Zimmer","year":"2023","journal-title":"Nat. Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8832\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:32:10Z","timestamp":1791203530000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,3]]},"references-count":28,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198832"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198832","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,3]]}}}