Immune Checkpoint Inhibitors in Merkel Cell Carcinoma of the Skin: A 2025 Comprehensive Review

Area of Science:

• Oncology
• Dermatology
• Immunology

Background:

• Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer.
• Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has significantly impacted MCC management.
• Limited published data necessitates a comprehensive review of ICIs in MCC treatment.

Purpose of the Study:

• To evaluate current evidence on immune checkpoint inhibitors (ICIs) in Merkel cell carcinoma (MCC).
• To compare ICI efficacy with other treatment modalities like surgery and radiotherapy.
• To assess ICI outcomes in neoadjuvant, adjuvant, and primary therapy settings for MCC.

Main Methods:

• Systematic review adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
• Manual search of Scopus, ScienceDirect, PubMed, and MEDLINE databases.
• Inclusion of peer-reviewed articles published between January 2000 and August 2025 using specific keywords.

Main Results:

• Neoadjuvant nivolumab showed a 54.5% response rate in the CheckMate 358 trial.
• Adjuvant nivolumab improved disease-free survival (ADMEC-O trial); adjuvant avelumab and pembrolizumab trials are ongoing (ADAM, STAMP).
• First-line pembrolizumab or avelumab yielded a 60% overall response rate and ~40% 3-year progression-free survival (KEYNOTE-017, JAVELIN trials).

Conclusions:

• Immune checkpoint inhibitors (ICIs) demonstrate encouraging efficacy in Merkel cell carcinoma (MCC) across various treatment settings.
• Optimizing treatment timing and integrating ICIs with multimodal therapies are crucial for future MCC management.
• Continued research is essential to further refine the role of ICIs in MCC.