{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T01:17:16Z","timestamp":1793582236559,"version":"4.5.0"},"reference-count":31,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"unspecified","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Albert Einstein College of Medicine Office of Medicine Student Research","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Kelsey Dickson Team Science Courage Research Award: Advancing New Therapies for Merkel Cell Carcinoma","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"National Institutes of Health\/National Cancer Institute, MD, USA","award":["P01 CA225517"],"award-info":[{"award-number":["P01 CA225517"]}]},{"name":"National Institutes of Health\/National Cancer Institute, MD, USA","award":["P30 CA015704"],"award-info":[{"award-number":["P30 CA015704"]}]},{"name":"MCC Patient Gift Fund at UW","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,8,25]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Merkel cell carcinoma is an aggressive skin cancer that progresses to advanced\/metastatic disease in ~40% of patients. First-line immune checkpoint inhibitors (ICI) that block the programmed cell death protein-1\/programmed death-ligand 1 axis provide 3-year progression-free responses in only ~40% of patients. The relative efficacy of salvage therapies in this setting is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a prospectively enrolled single-center cohort, 106 patients had disease progression during or shortly after ICI and received at least one local or systemic salvage therapy. Baseline disease characteristics, treatments, and outcomes data were collected. Patients were stratified by primary resistance (no response to initial ICI) or acquired resistance (loss of ICI response after initial benefit). Primary outcomes were progression-free survival (PFS) and disease-specific survival (DSS). Associations between salvage therapies and outcomes were evaluated using Cox models with time-varying covariates for treatments and adjustments for disease burden and ICI resistance type.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this cohort, 44 patients (42%) met criteria for primary resistance and 31 (29%) had acquired resistance. Median PFS from salvage initiation was more than double for patients with acquired versus primary resistance (9.5 vs 4.7 months; p=0.006). Median DSS was not reached for acquired resistance and 14.3 months for primary resistance (p=0.006). A minority of patients (n=14) survived \u22653 years after salvage initiation, typically following customized, multimodal salvage strategies. Among salvage regimens (ICI alone, ICI+radiation therapy (RT), chemotherapy, chemotherapy+ICI), only ICI+RT had a statistically significant association with improved DSS relative to ICI alone (after adjustment, including disease burden and ICI resistance type: adjusted HR 0.35, 95%\u2009CI 0.14 to 0.91).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with acquired resistance receiving salvage therapy have improved survival compared with those with primary resistance. While the addition of radiation to ICI was clearly associated with improved DSS, there continues to be a major need for new approaches to address ICI-resistant disease. Nevertheless, a durable benefit in select patients is possible via sequential, individualized, multidisciplinary treatments. We anticipate these data will be relevant for the design of clinical trials for this challenging ICI-resistant setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012660","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T05:40:18Z","timestamp":1758260418000},"page":"e012660","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Real-world outcomes of patients receiving salvage therapies for immune checkpoint inhibitor-resistant Merkel cell carcinoma: a rationale for future clinical trials"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0802-0279","authenticated-orcid":false,"given":"Peter Y","family":"Ch\u2019en","sequence":"first","affiliation":[{"name":"Dermatology, University of Washington, Seattle, Washington, USA"},{"name":"Albert Einstein College of Medicine, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6460-5871","authenticated-orcid":false,"given":"Yuzheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutch Cancer Center, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2427-4404","authenticated-orcid":false,"given":"Daniel S","family":"Hippe","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutch Cancer Center, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4525-6408","authenticated-orcid":false,"given":"Tomoko","family":"Akaike","sequence":"additional","affiliation":[{"name":"Dermatology, University of Washington, Seattle, Washington, USA"},{"name":"Fred Hutch Cancer Center, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2467-1349","authenticated-orcid":false,"given":"Natalie J","family":"Miller","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, Washington, USA"},{"name":"Hematology and Oncology, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1582-8292","authenticated-orcid":false,"given":"Candice","family":"Church","sequence":"additional","affiliation":[{"name":"Dermatology, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2697-268X","authenticated-orcid":false,"given":"Kristina","family":"Lachance","sequence":"additional","affiliation":[{"name":"Dermatology, University of Washington, Seattle, Washington, 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