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Immune Checkpoint Inhibitors and Beyond: An Overview of Immune-Based Therapies in Merkel Cell Carcinoma

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Abstract

Merkel cell carcinoma (MCC) is an aggressive skin cancer. Until 2017, patients with advanced disease were typically treated with conventional chemotherapies, with a median response duration of 3 months. Increased evidence of the role of the immune system in controlling this cancer has paved the way for immune-based therapies, with programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitors at the frontline. Avelumab, an anti-PD-L1 antibody, was the first-ever drug approved in advanced MCC after showing meaningful efficacy in a second-line setting. Objective responses were observed in one-third of patients and, most importantly, were durable with half of patients and one-third of patients still alive at 1 and 2 years, respectively. When used in a first-line setting, PD-1/PD-L1 inhibitors (avelumab, pembrolizumab, nivolumab) are even more promising as objective responses are observed in approximately 50–70% of patients within the first 4–8 weeks of treatment. Safety profiles are acceptable with 10–20% of patients experiencing adverse events grade ≥ 3. PD-1/PD-L1 inhibitors are considered the standard of care in advanced MCC and are currently being investigated in the adjuvant and neoadjuvant settings. However, innovative treatments are still needed in the metastatic setting, as approximately 50% of these patients will not persistently respond to currently available immunotherapies, and no predictors of response are available yet. Therefore, other immunotherapeutic strategies are now being investigated—ideally in combinations—to enhance the various aspects of the immune response against tumoral cells.

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Authors and Affiliations

  1. Dermatology Department, University Hospital of Tours, Avenue de la République, 37170, Chambray-les-Tours, France

    Mahtab Samimi

  2. “Biology of Polyomaviruses” Team, ISP 1282, INRA University of Tours, Tours, France

    Mahtab Samimi

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  1. Mahtab Samimi
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Correspondence to Mahtab Samimi.

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No external funding was used in the preparation of this review.

Conflict of interest

Mahtab Samimi has received speaking fees in educational programs from BMS, Janssen, Acthelion, and Abbvie.

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Samimi, M. Immune Checkpoint Inhibitors and Beyond: An Overview of Immune-Based Therapies in Merkel Cell Carcinoma. Am J Clin Dermatol 20, 391–407 (2019). https://doi.org/10.1007/s40257-019-00427-9

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  • DOI: https://doi.org/10.1007/s40257-019-00427-9

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