{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:52:27Z","timestamp":1787169147526,"version":"build-2736575974"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"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":"\n Background<\/jats:title>\n Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous malignancy. Immune checkpoint inhibition (ICI) with PD-(L)1 blockade has significantly improved treatment outcomes in metastatic disease. In patients with primary resistance to PD-(L)1 inhibition, a high overall response rate (ORR) of 50% to later-line ipilimumab plus nivolumab (IPI\/NIVO) has been demonstrated. However, clinical data on patients with progression after an initial response to IPI\/NIVO are still lacking.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Clinical data of three metastatic MCC patients who were re-exposed to IPI\/NIVO after progression were retrospectively evaluated.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Two of the three patients showed primary resistance to avelumab with progressive disease, while one patient showed complete response (according to RECIST V.1.1). All three patients received combined ICI with IPI\/NIVO as subsequent therapy, resulting in an ORR of \u223c 67%. However, all three patients progressed during follow-up and were re-exposed to IPI\/NIVO. With a follow-up period ranging from 6.5 to 37.1 months, no PFS event has been detected. ORR for IPI\/NIVO re-exposition was equal to that of initial IPI\/NIVO treatment.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In this retrospective follow-up analysis, we observed a response rate of 67% and long-lasting responses after re-exposition to combined ICI in metastatic MCC patients with progression after initial response or disease control upon their first IPI\/NIVO treatment. An important observation from this small analysis is that primary resistance to PD-L1 inhibition may result in a better response to IPI\/NIVO.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1495004","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T01:30:24Z","timestamp":1733362224000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Re-exposition to ipilimumab plus nivolumab in metastatic Merkel cell carcinoma"],"prefix":"10.3389","volume":"15","author":[{"given":"Valerie","family":"Glutsch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Schummer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Goebeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Gesierich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Schilling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17077","DOI":"10.1038\/nrdp.2017.77","article-title":"Merkel cell carcinoma","volume":"3","author":"Becker","year":"2017","journal-title":"Nat Rev Dis 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Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0000000000000432","article-title":"A retrospective study of ipilimumab plus nivolumab in anti-PD-L1\/PD-1 refractory merkel cell carcinoma","volume":"45","author":"Shalhout","year":"2022","journal-title":"J Immunother"},{"key":"B9","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.ejca.2017.01.009","article-title":"Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma","volume":"75","author":"Zimmer","year":"2017","journal-title":"Eur J Cancer"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01659-2","article-title":"Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial","volume":"400","author":"Kim","year":"2022","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined nivolumab and ipilimumab or monotherapy in untreated melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N Engl J Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30151-2","article-title":"Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial","volume":"20","author":"Rozeman","year":"2019","journal-title":"Lancet Oncol"}],"container-title":["Frontiers in 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