{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T18:51:34Z","timestamp":1773687094552,"version":"3.50.1"},"reference-count":33,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2020,8,25]]},"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Metastatic Merkel cell carcinoma (mMCC) is an aggressive neuroendocrine malignancy of the skin with a poor prognosis. Immune checkpoint inhibitors (ICIs) have shown substantial efficacy and favorable safety in clinical trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Medical records of patients (pts) with mMCC treated with ICIs from August 2015 to December 2018 at Peter MacCallum Cancer Centre in Australia were analyzed. Response was assessed with serial imaging, the majority with FDG-PET\/CT scans. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples was performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>23 pts with mMCC were treated with ICIs. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 6 pts. Objective responses (OR) were observed in 14 pts (61%): 10 (44%) complete responses (CR) and 4 (17%) partial responses (PR). Median time to response was 8 weeks (range 6 to 12) and 12-month progression-free survival rate was 39%. Increased OR were seen in pts aged less than 75 (OR 80% vs 46%), no prior history of chemotherapy (OR 64% vs 50%), patients with an immune-related adverse event (OR 100% vs 43%) and in MCPyV-negative tumors (OR 69% vs 43%). Pts with a CR had lower mean metabolic tumor volume on baseline FDG-PET\/CT scan (CR: 35.7 mL, no CR: 187.8 mL, p=0.05). There was no correlation between PD-L1 positivity and MCPyV status (p=0.764) or OR (p=0.245). 10 pts received radiation therapy (RT) during ICI: 4 pts started RT concurrently (OR 75%, CR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. Overall, 6 pts (26%) had grade 1\u20132 immune-related adverse events.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>ICIs showed efficacy and safety in mMCC consistent with trial data. Clinical and imaging predictors of response were identified.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2020-000700","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T17:52:31Z","timestamp":1602784351000},"page":"e000700","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical, FDG-PET and molecular markers of immune checkpoint inhibitor response in patients with metastatic Merkel cell carcinoma"],"prefix":"10.1136","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3769-490X","authenticated-orcid":false,"given":"Alison M","family":"Weppler","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Pattison","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prachi","family":"Bhave","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"De Ieso","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanette","family":"Raleigh","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athena","family":"Hatzimihalis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J","family":"Gill","sequence":"additional","affiliation":[{"name":"Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia"},{"name":"Department of Anatomical Pathology, University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiva","family":"Balachander","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Callahan","sequence":"additional","affiliation":[{"name":"Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Chua","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Au-Yeung","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant A","family":"McArthur","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodney J","family":"Hicks","sequence":"additional","affiliation":[{"name":"Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W","family":"Tothill","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"},{"name":"Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahneen","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"2025100301592053000_8.2.e000700.1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-016-5266-4"},{"key":"2025100301592053000_8.2.e000700.2","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1002\/cam4.815","article-title":"Response rates and durability of chemotherapy among 62 patients with metastatic Merkel cell carcinoma","volume":"5","author":"Iyer","year":"2016","journal-title":"Cancer Med"},{"key":"2025100301592053000_8.2.e000700.3","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1877"},{"key":"2025100301592053000_8.2.e000700.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1152586"},{"key":"2025100301592053000_8.2.e000700.5","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s11523-018-0585-y","article-title":"Treatment of advanced Merkel cell carcinoma: current therapeutic options and novel immunotherapy approaches","volume":"13","author":"Femia","year":"2018","journal-title":"Target Oncol"},{"key":"2025100301592053000_8.2.e000700.6","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-018-0571-4"},{"key":"2025100301592053000_8.2.e000700.7","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0310-x"},{"key":"2025100301592053000_8.2.e000700.8","doi-asserted-by":"crossref","DOI":"10.1001\/jamaoncol.2018.0077","article-title":"Efficacy and safety of first-line avelumab treatment in patients with stage IV metastatic Merkel cell carcinoma: a preplanned interim analysis of a clinical trial","volume":"4","author":"D'Angelo","year":"2018","journal-title":"JAMA Oncol"},{"key":"2025100301592053000_8.2.e000700.9","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1200\/JCO.18.01896","article-title":"Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy","volume":"37","author":"Nghiem","year":"2019","journal-title":"J Clin Oncol"},{"key":"2025100301592053000_8.2.e000700.10","doi-asserted-by":"crossref","first-page":"122S","DOI":"10.2967\/jnumed.108.057307","article-title":"From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors","volume":"50 Suppl 1","author":"Wahl","year":"2009","journal-title":"J Nucl Med"},{"key":"2025100301592053000_8.2.e000700.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"2025100301592053000_8.2.e000700.12","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.jtho.2018.05.013","article-title":"PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of Blueprint Phase 2 Project","volume":"13","author":"Tsao","year":"2018","journal-title":"J Thorac Oncol"},{"key":"2025100301592053000_8.2.e000700.13","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0215-8"},{"key":"2025100301592053000_8.2.e000700.14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1001\/jamadermatol.2015.2707","article-title":"Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab","volume":"152","author":"Hua","year":"2016","journal-title":"JAMA Dermatol"},{"key":"2025100301592053000_8.2.e000700.15","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1001\/jamadermatol.2015.1916","article-title":"Pembrolizumab cutaneous adverse events and their association with disease progression","volume":"151","author":"Sanlorenzo","year":"2015","journal-title":"JAMA Dermatol"},{"key":"2025100301592053000_8.2.e000700.16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1136"},{"key":"2025100301592053000_8.2.e000700.17","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-4159"},{"key":"2025100301592053000_8.2.e000700.18","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6494"},{"key":"2025100301592053000_8.2.e000700.19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1713444."},{"key":"2025100301592053000_8.2.e000700.20","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.115.158261"},{"key":"2025100301592053000_8.2.e000700.21","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1097\/MNM.0000000000000523","article-title":"Metabolic assessment of Merkel cell carcinoma: the role of 18F-FDG PET\/CT","volume":"37","author":"Ben-Haim","year":"2016","journal-title":"Nucl Med Commun"},{"key":"2025100301592053000_8.2.e000700.22","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1200\/JCO.2017.75.6270","article-title":"Durable complete response after discontinuation of pembrolizumab in patients with metastatic melanoma","volume":"36","author":"Robert","year":"2018","journal-title":"J Clin Oncol"},{"key":"2025100301592053000_8.2.e000700.23","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3340"},{"key":"2025100301592053000_8.2.e000700.24","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-019-07338-3"},{"key":"2025100301592053000_8.2.e000700.25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/149185","article-title":"Chronic inflammation and cytokines in the tumor microenvironment","volume":"2014","author":"Landskron","year":"2014","journal-title":"J Immunol Res"},{"key":"2025100301592053000_8.2.e000700.26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.canlet.2019.05.021","article-title":"Impact of hypoxic tumor microenvironment and tumor cell plasticity on the expression of immune checkpoints","volume":"458","author":"Lequeux","year":"2019","journal-title":"Cancer Lett"},{"key":"2025100301592053000_8.2.e000700.27","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.124989","article-title":"Tumor cell oxidative metabolism as a barrier to PD-1 blockade immunotherapy in melanoma","volume":"4","author":"Najjar","year":"2019","journal-title":"JCI Insight"},{"key":"2025100301592053000_8.2.e000700.28","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/680410"},{"key":"2025100301592053000_8.2.e000700.29","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0103"},{"key":"2025100301592053000_8.2.e000700.30","doi-asserted-by":"crossref","first-page":"18","DOI":"10.21105\/joss.00018","article-title":"Xenomapper: mapping reads in a mixed species context","volume":"1","author":"J. Wakefield","year":"2016","journal-title":"JOSS"},{"key":"2025100301592053000_8.2.e000700.31","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0539-0"},{"key":"2025100301592053000_8.2.e000700.32","doi-asserted-by":"crossref","unstructured":"Alexandrov L , Kim J , Haradhvala NJ , et al . The repertoire of mutational signatures in human cancer. BioRxiv 2018:322859.","DOI":"10.1101\/322859"},{"key":"2025100301592053000_8.2.e000700.33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1015"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2020-000700","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T08:59:29Z","timestamp":1759481969000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2020-000700"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10]]},"references-count":33,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,10,15]]},"published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1136\/jitc-2020-000700"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2020-000700","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10]]}}}