Immune checkpoint inhibition in Merkel cell carcinoma

Abstract

Merkel cell carcinoma (MCC) is arare but aggressive form of skin cancer in which Merkel cell polyomavirus infection and chronic exposure to ultraviolet radiation are key risk factors. Immune checkpoint inhibition has revolutionized the treatment of locally advanced, inoperable and metastatic MCC. To outline the modern management of MCC based on advances in our understanding of MCC tumour biology and the development of immune checkpoint inhibitors, namely inhibitors of programmed cell death protein (PD)-1- and PD‑1 ligand1 (PD-L1). Areview of the scientific literature listed in PubMed. First line therapy with the PD-L1 blocking antibody avelumab is associated with aresponse rate of 62%. In the second line setting, for example after chemotherapy, the response rate only reaches 33%. However, in patients who responded in the second line setting, 69% remained relapse free after 2years. Treatment responses occurred on average after 6.1weeks of therapy. First line treatment with pembrolizumab (anti-PD‑1 antibody) is associated with a2-year survival rate of 69% and the median survival rate has not been reached. Whilst the various chemotherapy regimens are associated with similar response rates, these are typically short lived. Checkpoint inhibition offers an effective treatment option for patients with MCC. Avelumab is currently licensed as atreatment for metastatic disease. Chemotherapy remains an option to reduce tumor load, or in the context of resistance and/or contraindications to immune checkpoint therapy. Adjuvant and neoadjuvant use of checkpoint inhibition in MCC may represent afuture treatment strategy pending the results of on-going clinical trials.