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CR: complete response CT: computed tomography FDA: US Food and Drug Administration ICB: immune checkpoint blockade MCC: Merkel cell carcinoma MCPyV: Merkel cell polyomavirus ORR: objective response rate PD-L1: programmed death ligand 1 PFS: progression-free survival PET: positron emission tomography SUV: standardized uptake values TVEC: talimogene laherparepvec INTRODUCTION Merkel cell carcinoma (MCC) is a rare, aggressive malignancy derived from cutaneous neuroendocrine cells perceiving light touch. MCC usually presents in elderly patients on sun-exposed areas, most commonly of the head and neck. Merkel cell polyomavirus (MCPyV) is directly involved in the pathogenesis of 80% of MCCs in which clonal integration results in expression of 2 key antigenic oncoproteins. MCPyV-negative tumors harbor many ultraviolet signature mutations with high levels of infiltrating T lymphocytes and programmed death ligand 1 (PD-L1) expression. MCC is thus an attractive target for immunotherapy because viruspositive tumors express foreign oncoproteins, and virus-negative tumors carry ultraviolet signature mutations providing noneself-epitopes for immune recognition. Historically, metastatic MCC was treated with chemotherapy. Although objective response rates (ORR) exceeded 50%, median progression-free survival (PFS) was approximately 3 months with no clear overall survival benefit. Recent phase II trials of immune checkpoint blockade (ICB) in advanced MCC targeting PD-1 with pembrolizumab or nivolumab or PD-L1 with avelumab have shown ORR of 65% in treatment-na€ıve patients and 40% following chemotherapy with PFS substantially superior to chemotherapy. However, fewer than 20% of patients achieve complete responses (CR), and the largest

Talimogene laherparepvec induces durable response of regionally advanced Merkel cell carcinoma in 4 consecutive patients