Update Merkel-Zell-Karzinom

Merkel cell carcinoma (MCC) is a rare subtype of skin cancer with neuroendocrine differentiation. Pathogenetically, either integration of the Merkel cell polyomavirus or UV damage of the cells play a role. This leads to high immunogenicity of the cells due to the expression of viral proteins or UV-induced neoantigens.

Summary of the current management of MCC

Literature search and own experience

Although MCC is potentially recognizable by the immune system, growth is often aggressive with high metastatic potential. However, data on the spontaneous course of MCC are rare, and detailed clinical data from registries are lacking. In the inoperable metastatic setting, cytotoxic chemotherapies were used in the past. Response rates were only short-lasting, and median progression-free survival was 3 months. On the basis of the potential immunogenicity of MCC, checkpoint inhibitors were tested and showed efficacy in prospective trials with long-lasting responses at least in a subgroup of patients. Four PD-1/PD-L1 immune-checkpoint inhibitors were tested, avelumab, pembrolizumab, nivolumab and retifanlimab. Due to the low incidence of MCC, these studies were only single-arm trials without comparison of different modalities. In the case of primary or secondary resistance to checkpoint blockade in the inoperable setting, experience is scarce. In the adjuvant situation, nivolumab treatment resulted in improved recurrence-free survival as compared to observation (reference). For the neoadjuvant situation, there are only few data; controlled studies are ongoing.

MCC is a highly aggressive skin cancer. In advanced stages, PD-1-/PD-L1-directed checkpoint blockade is the standard therapy. Initial positive data also suggest efficacy in the adjuvant and neoadjuvant situation. Further results from clinical trials are pending.