{"entity":{"id":"merkel-cell-carcinoma","kind":"cancer","name":"Merkel cell carcinoma","aka":[],"tldr":"Merkel cell carcinoma is a rare, fast-growing skin cancer, usually caused by a common virus (Merkel cell polyomavirus) or by sun damage. Once it had spread there was no treatment that worked; PD-1/PD-L1 immunotherapy now gives lasting responses in about half of patients.","summary":"Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer of older, fair-skinned and immunosuppressed people. About 80% of cases in the Northern Hemisphere are driven by clonally integrated Merkel cell polyomavirus (MCPyV, discovered 2008); the remainder are UV-induced with a very high tumour mutational burden. Both forms are immunogenic, which explains why MCC responded to checkpoint blockade when chemotherapy gave only brief responses.\n\nLocalised disease is treated with wide excision, sentinel node biopsy and adjuvant radiotherapy; the STAMP and ADMEC-O trials tested adjuvant PD-1 blockade, with ADMEC-O (nivolumab) showing a disease-free survival benefit in 2023. Metastatic disease is treated first line with avelumab (JAVELIN Merkel 200, first approval 2017), pembrolizumab (KEYNOTE-017, 2018) or retifanlimab (POD1UM-201, 2023); durable responses occur in about half, and chemotherapy is reserved for immunotherapy failure. Circulating MCPyV oncoprotein antibodies (AMERK) allow surveillance in seropositive patients.\n\nUnsolved: primary and acquired immunotherapy resistance (about half of patients), immunosuppressed patients (transplant, CLL) who cannot receive checkpoint blockade safely, and the adjuvant standard.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Merkel-cell_carcinoma","links":[{"label":"NCCN Guidelines: Merkel Cell Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1444"},{"label":"Merkelcell.org (UW/Fred Hutch)","url":"https://merkelcell.org/"},{"label":"NCI PDQ: Merkel cell carcinoma","url":"https://www.cancer.gov/types/skin/patient/merkel-cell-treatment-pdq"},{"label":"Keohane, Proby, Newlands, Motley, Nasr and Mohd Mustapa, British Journal of Dermatology 2018;179:824 to 828: the new 8th edition of TNM staging and its implications for skin cancer, a review by the British Association of Dermatologists and the Royal College of Pathologists, UK","url":"https://doi.org/10.1111/bjd.16892"},{"label":"van Bodegraven et al., British Journal of Dermatology 2023;188(6):777 to 784: 'Get Data Out' Skin, national cancer registry incidence and survival rates for all registered skin tumour groups for 2013 to 2019 in England","url":"https://doi.org/10.1093/bjd/ljad033"}],"tags":["gap-fill","skin","rare"],"related":["basal-cell-carcinoma","cutaneous-scc","melanoma"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","sentinel-node","imrt-igrt","oncolytic-virus","tcr-t"],"targets":["pd1","pdl1","ctla4"],"drugs":["avelumab","pembrolizumab","retifanlimab","nivolumab","ipilimumab","platinum-etoposide","talimogene-laherparepvec"],"companies":["merck","pfizer","incyte","bms","neonc-technologies"],"institutions":[],"pathways":["pd1-checkpoint","p53-cell-cycle"],"terms":["tmb","irae","mcpyv-status","keratinocyte-cancer","keratinocyte-cancer-counting","tnm-skin-carcinoma","skin-cancer-high-risk-features","radiotherapy-for-skin-cancer","skin-cancer-after-organ-transplant","surgical-margins-keratinocyte-cancer"],"trials":["nct06947928","stamp-merkel","checkmate-358","pod1um-201","admec-o"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Merkel cell carcinoma is not a keratinocyte cancer, and it is staged by a different chapter. It arises from Merkel cells rather than keratinocytes, and both the UICC and AJCC give it its own staging chapter, separate from the cutaneous carcinoma chapters that cover basal cell, squamous cell and adnexal carcinoma; the UK skin carcinoma staging appendix excludes it in terms. Sentinel node biopsy is written into its pathological nodal staging, and for both melanoma and Merkel cell carcinoma the clinician must state whether involved nodes were clinically occult or clinically detected (Keohane 2018). It is caught by the phrase non-melanoma skin cancer in some statistics, including mortality figures published for that group, which is one reason the field is moving to the more precise term keratinocyte cancer for the two common ones."],"group":"skin","burden":"Merkel cell carcinoma causes about 3,000 cases per year in the US and rising; median age is ~75; it is roughly 40 times rarer than melanoma and more likely to spread stage for stage, which is why immunotherapy's durable responses mattered so much.","subtypes":["Virus-positive MCC (MCPyV, ~80%)","Virus-negative UV-driven MCC (high TMB, RB1/TP53 mutations)","MCC in immunosuppressed patients (transplant, CLL, HIV)"],"biomarkers":["CK20 perinuclear dot staining; TTF-1 negative","MCPyV large T antigen (IHC/PCR)","MCPyV oncoprotein antibody titre (surveillance)","Sentinel lymph node status","PD-L1 (not required for treatment)","Tumour mutational burden (virus-negative)"],"standardOfCare":[{"setting":"Localised (stage I-II)","approach":"Wide local excision with sentinel node biopsy; adjuvant radiotherapy to the primary site (and nodal basin if node-positive); adjuvant nivolumab supported by ADMEC-O in selected patients.","refs":["sentinel-node","imrt-igrt","nivolumab"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Merkel Cell Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1444"}},{"setting":"Regional nodal disease (stage III)","approach":"Lymphadenectomy and/or nodal radiotherapy; neoadjuvant nivolumab (CheckMate 358) produced pathological complete responses in about half.","refs":["nivolumab","imrt-igrt"]},{"setting":"Metastatic, first line","approach":"Avelumab, pembrolizumab or retifanlimab; ~50% response with most responses durable.","refs":["avelumab","pembrolizumab","retifanlimab"],"guideline":{"nccn":"Category 2A (preferred)","version":"NCCN Guidelines: Merkel Cell Carcinoma"}},{"setting":"Immunotherapy-refractory","approach":"Platinum-etoposide chemotherapy (brief responses), radiotherapy, clinical trials (ipilimumab-nivolumab, T-VEC, adoptive T cells).","refs":["platinum-etoposide","ipilimumab","talimogene-laherparepvec"]},{"setting":"Choosing among the three PD-1 pathway antibodies","approach":"Avelumab, pembrolizumab and retifanlimab are all approved and none has been compared with another. First-line response was 39.7 per cent with avelumab in 116 patients, 56 per cent with pembrolizumab in 50 and 54.5 per cent with retifanlimab in 101. The retifanlimab study is the most fully reported: 17.8 per cent complete responses, median duration of response not reached in complete responders and 25.3 months in partial responders, median progression-free survival 16.0 months, and 63 per cent of patients alive at three years, in a disease where chemotherapy responses were measured in months. Grade 3 immune-related adverse events occurred in 10.9 per cent. Which antibody is used matters far less than that roughly half of patients respond and most responders keep responding.","refs":["pod1um-201","javelin-merkel-200","keynote-017","retifanlimab","avelumab","pembrolizumab","irae"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Merkel Cell Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1444"}},{"setting":"After complete resection: what the adjuvant evidence does and does not show","approach":"ADMEC-O randomised 179 patients with completely resected Merkel cell carcinoma 2 to 1 to a year of nivolumab or to observation. Disease-free survival was 85 per cent at 12 months and 84 per cent at 24 with nivolumab against 77 and 73 per cent with observation, a hazard ratio of 0.58 whose 95 per cent confidence interval, 0.30 to 1.12, crosses one; the authors state it as an absolute risk reduction of 9 and 10 percentage points. Grade 3 or 4 adverse events occurred in 42 per cent against 11 per cent. Overall survival had ten events against six in a group half the size and is not mature. This is a phase 2 signal in a rare disease, not a proven standard, and the randomised phase 3 that would settle it, STAMP, has not reported.","refs":["admec-o","stamp-merkel","nivolumab","irae"],"guideline":{"version":"ADMEC-O interim analysis (The Lancet 2023)","url":"https://doi.org/10.1016/s0140-6736(23)00769-9"}},{"setting":"What is available in England","approach":"NICE technology appraisal TA691 recommendation 1.1 recommends avelumab for metastatic Merkel cell carcinoma in adults who have not had chemotherapy for metastatic disease, under a commercial arrangement, on evidence collected in the Cancer Drugs Fund under TA517. TA517 recommendation 1.1 continues to cover its use after one or more lines of chemotherapy. Pembrolizumab and retifanlimab have no NICE appraisal for this disease.","refs":["avelumab","pembrolizumab","retifanlimab","javelin-merkel-200"],"guideline":{"version":"NICE TA691 recommendation 1.1 and NICE TA517 recommendation 1.1 (avelumab recommended)","url":"https://www.nice.org.uk/guidance/ta691"}}],"stateOfArt":["Three approved PD-1/PD-L1 antibodies; about half of metastatic patients respond and most responders stay in remission for years.","Virus-driven biology makes MCPyV antigens an appealing target for vaccines and TCR-T.","Adjuvant immunotherapy has its first positive trial (ADMEC-O) and is entering guidelines.","Serologic surveillance (MCPyV oncoprotein antibodies) reduces imaging in seropositive patients."],"history":[{"year":1972,"title":"Toker describes 'trabecular carcinoma of the skin'","refs":[]},{"year":2008,"title":"Merkel cell polyomavirus discovered","note":"Feng, Chang and Moore find clonally integrated MCPyV in most MCC using digital transcriptome subtraction.","refs":[]},{"year":2016,"title":"Pembrolizumab first-line phase 2 (KEYNOTE-017, NEJM)","refs":["pembrolizumab"]},{"year":2017,"title":"Avelumab: first approved therapy for MCC","note":"JAVELIN Merkel 200; accelerated approval March 2017.","refs":["avelumab"]},{"year":2018,"title":"Pembrolizumab approved","refs":["pembrolizumab"]},{"year":2023,"title":"Retifanlimab approved; ADMEC-O adjuvant nivolumab positive","refs":["retifanlimab","nivolumab"]},{"year":2023,"title":"ADMEC-O: the first randomised adjuvant signal","note":"179 patients randomised 2 to 1 to a year of nivolumab or observation; disease-free survival 84 against 73 per cent at 24 months, hazard ratio 0.58 with a confidence interval crossing one, and overall survival not mature.","refs":["admec-o"]},{"year":2025,"title":"POD1UM-201: a third PD-1 antibody with three-year follow-up","note":"Objective response 54.5 per cent in 101 chemotherapy-naive patients, median progression-free survival 16.0 months and 63 per cent alive at three years.","refs":["pod1um-201"]}],"pipeline":["nivolumab","retifanlimab","ipilimumab"],"openProblems":["Half of patients do not respond to PD-1 blockade and have no effective second line.","Immunosuppressed patients: high incidence, poor outcomes, contraindications to immunotherapy.","No validated adjuvant standard yet despite ADMEC-O.","Rarity limits trial size; registries (e.g. Seattle) carry much of the evidence.","Three PD-1 pathway antibodies are approved for this disease and none has ever been compared with another; the choice is made on availability and schedule rather than on evidence.","The adjuvant question rests on a phase 2 trial whose hazard ratio crosses one and whose survival data are not mature, and the phase 3 that would settle it has not reported."],"parent":"skin-cancer"},"route":"/cancers/merkel-cell-carcinoma/","neighbours":{"cancer":[{"id":"advanced-cutaneous-scc","kind":"cancer","name":"Advanced cutaneous squamous cell carcinoma","route":"/cancers/advanced-cutaneous-scc/"},{"id":"basal-cell-carcinoma","kind":"cancer","name":"Basal cell carcinoma","route":"/cancers/basal-cell-carcinoma/"},{"id":"cutaneous-scc","kind":"cancer","name":"Cutaneous squamous cell carcinoma","route":"/cancers/cutaneous-scc/"},{"id":"locally-advanced-bcc","kind":"cancer","name":"Locally advanced and metastatic basal cell carcinoma","route":"/cancers/locally-advanced-bcc/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"technology":[{"id":"electron-beam-therapy-systems","kind":"technology","name":"Electron beam therapy systems (linac electrons, total skin electron units, mobile electron IORT)","route":"/technologies/electron-beam-therapy-systems/"},{"id":"gamma-probes-dose-calibrators","kind":"technology","name":"Gamma probes, handheld gamma cameras and dose calibrators","route":"/technologies/gamma-probes-dose-calibrators/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"},{"id":"sentinel-node","kind":"technology","name":"Sentinel lymph node biopsy","route":"/technologies/sentinel-node/"},{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","route":"/technologies/tcr-t/"}],"target":[{"id":"ctla4","kind":"target","name":"CTLA-4","route":"/targets/ctla4/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"platinum-etoposide","kind":"drug","name":"Platinum + etoposide (EP / CE)","route":"/drugs/platinum-etoposide/"},{"id":"retifanlimab","kind":"drug","name":"Retifanlimab","route":"/drugs/retifanlimab/"},{"id":"talimogene-laherparepvec","kind":"drug","name":"Talimogene laherparepvec","route":"/drugs/talimogene-laherparepvec/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"},{"id":"incyte","kind":"company","name":"Incyte","route":"/companies/incyte/"},{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"},{"id":"merck-kgaa","kind":"company","name":"Merck KGaA (EMD Serono)","route":"/companies/merck-kgaa/"},{"id":"neonc-technologies","kind":"company","name":"Neonc Technologies","route":"/companies/neonc-technologies/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"pathway":[{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"},{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"term":[{"id":"tnm-skin-carcinoma","kind":"term","name":"How skin carcinoma is staged in Britain: UICC TNM, and why it is not the American system","route":"/terms/tnm-skin-carcinoma/"},{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"},{"id":"keratinocyte-cancer","kind":"term","name":"Keratinocyte cancer (and why 'non-melanoma skin cancer' is being retired)","route":"/terms/keratinocyte-cancer/"},{"id":"mcpyv-status","kind":"term","name":"Merkel cell polyomavirus (MCPyV) status","route":"/terms/mcpyv-status/"},{"id":"radiotherapy-for-skin-cancer","kind":"term","name":"Radiotherapy for skin cancer","route":"/terms/radiotherapy-for-skin-cancer/"},{"id":"rare-cancers","kind":"term","name":"Rare cancers","route":"/terms/rare-cancers/"},{"id":"skin-cancer-after-organ-transplant","kind":"term","name":"Skin cancer after an organ transplant","route":"/terms/skin-cancer-after-organ-transplant/"},{"id":"surgical-margins-keratinocyte-cancer","kind":"term","name":"The margin in skin cancer surgery","route":"/terms/surgical-margins-keratinocyte-cancer/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"},{"id":"skin-cancer-high-risk-features","kind":"term","name":"What makes a skin cancer high risk: the UK feature lists","route":"/terms/skin-cancer-high-risk-features/"},{"id":"keratinocyte-cancer-counting","kind":"term","name":"Why nobody knows how many skin cancers there are: the counting rule behind every figure","route":"/terms/keratinocyte-cancer-counting/"}],"trial":[{"id":"nct07302347","kind":"trial","name":"A Study of Pembrolizumab in Japanese Pediatric Participants With Solid Tumors or Lymphomas and Japanese Adult Participants With Merkel Cell Carcinoma (MK-3475-G21/KEYNOTE-G21)","route":"/trials/nct07302347/"},{"id":"nct07115043","kind":"trial","name":"A Study to Investigate Safety of AZD6750 in Adult Participants With Select Advanced or Metastatic Solid Tumors","route":"/trials/nct07115043/"},{"id":"admec-o","kind":"trial","name":"ADMEC-O (adjuvant nivolumab in completely resected Merkel cell carcinoma)","route":"/trials/admec-o/"},{"id":"nct05120271","kind":"trial","name":"BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors","route":"/trials/nct05120271/"},{"id":"checkmate-358","kind":"trial","name":"CheckMate 358","route":"/trials/checkmate-358/"},{"id":"javelin-merkel-200","kind":"trial","name":"JAVELIN Merkel 200","route":"/trials/javelin-merkel-200/"},{"id":"keynote-017","kind":"trial","name":"KEYNOTE-017 (Cancer Immunotherapy Trials Network 09)","route":"/trials/keynote-017/"},{"id":"nct06947928","kind":"trial","name":"Placebo-Controlled Trial of IFx-Hu2.0 Followed By Pembrolizumab In Checkpoint Inhibitor Naïve Participants With Advanced Or Metastatic Merkel Cell Car","route":"/trials/nct06947928/"},{"id":"pod1um-201","kind":"trial","name":"POD1UM-201 (retifanlimab in advanced Merkel cell carcinoma)","route":"/trials/pod1um-201/"},{"id":"nct03228667","kind":"trial","name":"QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors","route":"/trials/nct03228667/"},{"id":"mcc-rational-treatment","kind":"trial","name":"Rational treatment selection for Merkel cell carcinoma","route":"/trials/mcc-rational-treatment/"},{"id":"nct06047379","kind":"trial","name":"Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis","route":"/trials/nct06047379/"},{"id":"stamp-merkel","kind":"trial","name":"STAMP (EA6174)","route":"/trials/stamp-merkel/"},{"id":"nct04349436","kind":"trial","name":"Study to Investigate the Efficacy and Safety of RP1 in Adult Patients With Organ Transplants and Advanced Skin Malignancies","route":"/trials/nct04349436/"}],"person":[{"id":"dirk-schadendorf","kind":"person","name":"Dirk Schadendorf","route":"/people/dirk-schadendorf/"},{"id":"howard-kaufman","kind":"person","name":"Howard L. Kaufman","route":"/people/howard-kaufman/"},{"id":"reinhard-dummer","kind":"person","name":"Reinhard Dummer","route":"/people/reinhard-dummer/"},{"id":"sandra-dangelo","kind":"person","name":"Sandra P. D'Angelo","route":"/people/sandra-dangelo/"},{"id":"shailender-bhatia","kind":"person","name":"Shailender Bhatia","route":"/people/shailender-bhatia/"}],"institution":[{"id":"guys-st-thomas","kind":"institution","name":"Guy's and St Thomas' NHS Foundation Trust / King's Health Partners Cancer Centre","route":"/institutions/guys-st-thomas/"},{"id":"birmingham-cancer-centre","kind":"institution","name":"University Hospitals Birmingham / University of Birmingham Cancer Research Centre","route":"/institutions/birmingham-cancer-centre/"},{"id":"upmc-hillman","kind":"institution","name":"UPMC Hillman Cancer Center","route":"/institutions/upmc-hillman/"}],"journal":[{"id":"tumour-virus-research","kind":"journal","name":"Tumour virus research","route":"/journals/tumour-virus-research/"}]}}