{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:55:44Z","timestamp":1776318944922,"version":"3.50.1"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Metastatic melanoma has historically had a poor prognosis; however, survival has improved with immunotherapies, such as PD\u22121 and CTLA\u22124 inhibitors, and molecular targeted therapies for BRAF\u2212mutant tumors. The combination of nivolumab and ipilimumab is highly effective, though with increased rates of toxicity. In Italy, since January 2022, such therapeutic combination has been approved and reimbursed only for metastatic melanoma patients with brain metastases or with PD\u2212L1 expression &amp;lt;1%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a real-world study in six academic centers in southern Italy and analyzed the efficacy and toxicity outcomes in 72 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The response rate was 54% (39\/72) and, after 13.6 months of median follow-up, a longer median progression-free survival [17.03 months (95% CI 4.8-18.6)] compared to the pivotal CheckMate-067 trial or to other real-world studies. Better survival correlated with objective responses (p&amp;lt;0.0001) and low disease burden (less than three metastatic sites) (p=0.0415). All patients achieving an objective response had tumors with high or intermediatetumor mutational burden. The rates of immune-related adverse events were similar to those reported in the literature, but there was a lower therapy discontinuation rate. This might be due to more appropriate managing of emerging immunotherapy toxicities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1738772","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:25:45Z","timestamp":1776317145000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical activity and safety of nivolumab in combination with ipilimumab in metastatic melanoma: findings from REALIPINIVO, a real-world study"],"prefix":"10.3389","volume":"17","author":[{"given":"Francesco","family":"Caraglia","sequence":"first","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Argenziano","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Scala","sequence":"additional","affiliation":[{"name":"Clinical Medicine and Surgery, University of Naples Federico II","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Sparano","sequence":"additional","affiliation":[{"name":"Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Del Giudice","sequence":"additional","affiliation":[{"name":"Oncology Unit, Oncology Department, \u201cAzienda Ospedaliero Universitaria (AOU) Dulbecco\u201d Hospital","place":["Catanzaro, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Chiara","family":"Sergi","sequence":"additional","affiliation":[{"name":"Unit of Medical Oncology, \u201cMons. 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Dimiccoli\u201d Hospital","place":["Barletta, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Maria","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Azienda Ospedaliera di Rilievo Nazionale (AORN) San Pio","place":["Benevento, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Forte","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvana","family":"Cozzolino","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonino","family":"Colloca","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Cioli","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Ottaviano","sequence":"additional","affiliation":[{"name":"Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Iavarone","sequence":"additional","affiliation":[{"name":"PhD Course in Public Health, Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato","family":"Franco","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Scharf","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Cappabianca","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo Antonio","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerio","family":"Nardone","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Formisano","sequence":"additional","affiliation":[{"name":"Clinical Medicine and Surgery, University of Naples Federico II","place":["Naples, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","place":["Napoli, 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