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Merkel cell carcinoma

Merkel cell carcinoma is a rare, fast-growing skin cancer, usually caused by a common virus (Merkel cell polyomavirus) or by sun damage. It was almost untreatable once it spread; PD-1/PD-L1 immunotherapy now gives lasting responses in about half of patients.

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.

Localised 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.

Unsolved: primary and acquired immunotherapy resistance (about half of patients), immunosuppressed patients (transplant, CLL) who cannot receive checkpoint blockade safely, and the adjuvant standard.

State of the art today

  • 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.
Who it affects

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 but twice as lethal stage for stage.

Group
skin

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Localised (stage I-II)

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.

NCCN · Category 2A
Sentinel lymph node biopsyIMRT / IGRT (modern external beam)Nivolumab
Regional nodal disease (stage III)

Lymphadenectomy and/or nodal radiotherapy; neoadjuvant nivolumab (CheckMate 358) produced pathological complete responses in about half.

NivolumabIMRT / IGRT (modern external beam)
Metastatic, first line

Avelumab, pembrolizumab or retifanlimab; ~50% response with most responses durable.

NCCN · Category 2A (preferred)
AvelumabPembrolizumabRetifanlimab
Immunotherapy-refractory

Platinum-etoposide chemotherapy (brief responses), radiotherapy, clinical trials (ipilimumab-nivolumab, T-VEC, adoptive T cells).

Platinum + etoposide (EP / CE)IpilimumabTalimogene laherparepvec

Subtypes & biomarkers

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Subtypes
  • Virus-positive MCC (MCPyV, ~80%)
  • Virus-negative UV-driven MCC (high TMB, RB1/TP53 mutations)
  • MCC in immunosuppressed patients (transplant, CLL, HIV)
Biomarkers clinicians test

Target prevalence in this cancer

History

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  1. 1972Toker describes 'trabecular carcinoma of the skin'
  2. 2008Merkel cell polyomavirus discovered

    Feng, Chang and Moore find clonally integrated MCPyV in most MCC using digital transcriptome subtraction.

  3. 2016Pembrolizumab first-line phase 2 (KEYNOTE-017, NEJM)
    Pembrolizumab
  4. 2017Avelumab: first approved therapy for MCC

    JAVELIN Merkel 200; accelerated approval March 2017.

    Avelumab
  5. 2018Pembrolizumab approved
    Pembrolizumab
  6. 2023Retifanlimab approved; ADMEC-O adjuvant nivolumab positive
    RetifanlimabNivolumab

Pipeline

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ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
Not mapped hereAnti-PD-1 monoclonal antibody (IgG4)
Retifanlimab · Zynyz
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy

Open problems

  • 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.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Merkel cell carcinoma
condition: Merkel cell carcinoma
Open on ClinicalTrials.gov →

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Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Merkel cell carcinoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 17 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example CK20 perinuclear dot staining; TTF-1 negative, MCPyV large T antigen, MCPyV oncoprotein antibody titre, Sentinel lymph node status, PD-L1), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Virus-positive MCC, Virus-negative UV-driven MCC, MCC in immunosuppressed patients.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Localised (stage I-II)

  1. For my situation (localised (stage i-ii)), which of the standard options do you recommend and why?
    Why: Guideline options include: 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.
  2. Am I a candidate for Nivolumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Regional nodal disease (stage III)

  1. For my situation (regional nodal disease (stage iii)), which of the standard options do you recommend and why?
    Why: Guideline options include: Lymphadenectomy and/or nodal radiotherapy; neoadjuvant nivolumab (CheckMate 358) produced pathological complete responses in about half.
  2. Am I a candidate for Nivolumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic, first line

  1. For my situation (metastatic, first line), which of the standard options do you recommend and why?
    Why: Guideline options include: Avelumab, pembrolizumab or retifanlimab; ~50% response with most responses durable.
  2. Am I a candidate for Avelumab, Pembrolizumab, Retifanlimab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Immunotherapy-refractory

  1. For my situation (immunotherapy-refractory), which of the standard options do you recommend and why?
    Why: Guideline options include: Platinum-etoposide chemotherapy (brief responses), radiotherapy, clinical trials (ipilimumab-nivolumab, T-VEC, adoptive T cells).
  2. Am I a candidate for Platinum + etoposide (EP / CE), Ipilimumab, Talimogene laherparepvec, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

  1. Are there clinical trials I could join, for example of Nivolumab, Retifanlimab, Ipilimumab?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. Would a second opinion at a high-volume centre change anything, and can you help arrange it?
    Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
  3. What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
    Why: Supportive care improves quality of life and helps patients complete treatment.
  4. I read that “Half of patients do not respond to PD-1 blockade and have no effective second line”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Immunosuppressed patients: high incidence, poor outcomes, contraindications to immunotherapy”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

8
Cytotoxic chemotherapyImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Oncolytic virusesPlatinum agentsSentinel lymph node biopsyTCR-T cell therapyTopoisomerase-I inhibitors (and ADC payloads)

targets

3
CTLA-4PD-1PD-L1

drugs

7
ApprovedMonoclonal antibody (anti-PD-L1)
Avelumab · Bavencio
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Not mapped hereCytotoxic regimen
Platinum + etoposide (EP / CE)
Not mapped hereAnti-PD-1 monoclonal antibody (IgG4)
Retifanlimab · Zynyz
ApprovedOncolytic virus (HSV-1)
Talimogene laherparepvec · Imlygic

companies

5
AmgenBristol Myers SquibbIncyteMerck & Co. (MSD)Pfizer (incl. Seagen)

institutions

1
UPMC Hillman Cancer Center

pathways

3
Oncogenic virusesp53 / RB / cell-cycle checkpointPD-1 / PD-L1 immune checkpoint & T-cell activation

terms

3
Immune-related adverse events (irAEs)Rare cancersTumour mutational burden (TMB)

Latest papers

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Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Merkel cell carcinoma" OR ABSTRACT:"Merkel cell carcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Merkel cell carcinoma, not a curated reading list.

Connected

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Pages like this

not linked directly; found by shared links

technologies

5
Immune checkpoint inhibitorsIMRT / IGRT (modern external beam)Oncolytic virusesSentinel lymph node biopsyTCR-T cell therapy

targets

3
CTLA-4PD-1PD-L1

drugs

7
ApprovedMonoclonal antibody (anti-PD-L1)
Avelumab · Bavencio
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Not mapped hereCytotoxic regimen
Platinum + etoposide (EP / CE)
Not mapped hereAnti-PD-1 monoclonal antibody (IgG4)
Retifanlimab · Zynyz
ApprovedOncolytic virus (HSV-1)
Talimogene laherparepvec · Imlygic

companies

4
Bristol Myers SquibbIncyteMerck & Co. (MSD)Pfizer (incl. Seagen)

institutions

1
UPMC Hillman Cancer Center

pathways

3
Oncogenic virusesp53 / RB / cell-cycle checkpointPD-1 / PD-L1 immune checkpoint & T-cell activation

terms

3
Immune-related adverse events (irAEs)Rare cancersTumour mutational burden (TMB)