Immunotherapy for Merkel Cell Carcinoma

Opinion statementMerkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin, with frequent recurrences, metastasis, and a high mortality rate. For primary or locoregional MCC, a wide local excision followed by radiation therapy is the basic treatment modality for preventing recurrence at the primary site and involved lymph nodes. Cytotoxic chemotherapy has been commonly used to treat patients with metastatic MCC, but not as an adjuvant therapy for high-risk resected MCC. Although MCC is often chemotherapy-sensitive in the first-line setting, responses are rarely durable and most patients subsequently relapse and develop metastasis. Treatment with checkpoint inhibitors (CPIs) has shown a major advancement in the treatment of advanced MCC. Systemic therapy against programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) is associated with a high objective response rate (ORR), prolonged durable responses, and good tolerability in advanced-stage MCC. CPIs are now included in the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of patients with metastatic MCC. Multiple clinical trials of CPIs administered as monotherapy or in combination with other agents or modalities, including the adjuvant setting, are ongoing. Immunotherapy offers a promising future for patients with MCC. In this review, we present an overview of emerging data on immunotherapy, especially CPIs of the PD-1/PD-L1 pathway, for patients with advanced MCC.