Sequential Immune Checkpoint Inhibition in the Therapy of Merkel Cell Carcinoma

Abstract

Merkel cell carcinoma is associated with a high rate of mortality. Although more than fifty percent of patients with metastatic disease respond to immune checkpoint inhibition, the management of those who do not respond to programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition is unclear. We present a 67 year old male with Merkel cell carcinoma and histologically confirmed liver metastases, which developed five years after the initial diagnosis. Following first-line chemotherapy (Paclitaxel and Carboplatin) and disease progression, treatment with the immune checkpoint inhibitor Avelumab (anti-PD-L1 antibody) was commenced. Despite an initial response, staging examinations after 6 treatment cycles revealed that one of the liver metastases had increased in size and a partial liver resection was performed. Due to the subsequent development of new liver metastases, treatment with the PD-1 inhibitor Pembrolizumab was initiated. Stating examinations confirmed complete disease remission, which has now persisted for over 2 years. This clinical observation highlights the different mechanisms of action of PD-1 and PD-L1 inhibitors and could provide a rationale for sequential therapy in the treatment of metastatic Merkel cell carcinoma following disease progression which should be formally addressed in clinical trials.