Immune checkpoint blockade for Merkel cell carcinoma: actual findings and unanswered questions

  • Marco GalloEmail author
  • Valentina Guarnotta
  • Federica De Cicco
  • Manila Rubino
  • Antongiulio Faggiano
  • Annamaria Colao
  • NIKE Group
Review – Clinical Oncology



Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma arising from the skin. We aimed to review and deal with some of the most relevant controversial topics on the correct use of immunotherapy for the treatment of MCC.


The primary search was carried out via PubMed, EMBASE, and the Cochrane Library (until 31st May, 2018), while other articles and guidelines were retrieved from related papers or those referenced in these papers. Additionally, we performed an extensive search on to gather information on the ongoing clinical trials related to this specific topic.


We performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies evaluating these issues: Are there any predictive criteria of response to immunotherapy? What is the correct place of immunotherapy in the treatment algorithm of MCC? What is the best choice after immunotherapy failure? What to do with patients for whom immunotherapy is not been feasible or contraindicated? How long should immunotherapy be prolonged, and what follow-up should be offered after complete response?


The therapeutic landscape of MCC is rapidly evolving: many open issues will probably be resolved, and many other questions are likely to arise in the next few years. The results of ongoing prospective clinical trials and of several other studies on these issues are eagerly awaited.


Merkel cell carcinoma Neuroendocrine tumours Immune checkpoint inhibitors Avelumab Pembrolizumab Therapy 



This review is part of the ‘NIKE’ project (Neuroendocrine tumours Innovation Knowledge and Education) led by Prof Annamaria Colao, which aims at increasing the knowledge on NETs. We would like to acknowledge all the Collaborators of this project: Manuela Albertelli, Barbara Altieri, Elena Ambrosetti, Antonio Bianchi, Lena Bottiglieri, Severo Campione, Silvia Carra, Carla Di Dato, Sergio Di Molfetta, Antonella Di Sarno, Giuseppe Fanciulli, Diego Ferone, Francesco Ferraù, Elisa Giannetta, Federica Grillo, Erika Maria Grossrubatscher, Elia Guadagno, Andrea Isidori, Fabio Lo Calzo, Pasqualino Malandrino, Chiara Martini, Erika Messina, Roberta Modica, Giovanna Muscogiuri, Genoveffa Pizza, Paola Razzore, Laura Rizza, Rosaria Maddalena Ruggeri, Concetta Sciammarella, Giovanni Vitale, and Maria Chiara Zatelli.

Author contributions

All authors have contributed equally to the conception and design of the review. MG, FDC, VG, and MR analyzed data and drafted the article. AF and AC revised the manuscript critically. All authors approved the final article.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Oncological Endocrinology Unit, Department of Medical SciencesUniversity of TurinTurinItaly
  2. 2.Section of Endocrine-Metabolic Diseases, Biomedical Department of Internal and Specialist Medicine (DIBIMIS)University of PalermoPalermoItaly
  3. 3.Department of Clinical Medicine and SurgeryUniversity “Federico II”NaplesItaly
  4. 4.Unit of Gastrointestinal Medical Oncology and Neuroendocrine TumoursEuropean Institute of Oncology, IEOMilanItaly

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