Merkel Cell Carcinoma: An Immunotherapy Fairy-Tale?

Enrica Teresa Tanda,Agostina Lagodin D’Amato,Giovanni Rossi,Paola Queirolo,Federica Cecchi,Elena Croce,Andrea Boutros,Francesco Spagnolo

doi:10.3389/fonc.2021.739006

Abstract

Merkel cell carcinoma (MCC) is a rare, highly aggressive, neuroendocrine cutaneous tumor. The incidence of MCC is growing worldwide, and the disease-related mortality is about three-fold higher than melanoma. Since a few years ago, very little has been known about this disease, and chemotherapy has been the standard of care. Nowadays, new discoveries about the pathophysiology of this neoplasm and the introduction of immunotherapy allowed to completely rewrite the history of these patients. In this review, we provide a summary of the most important changes in the management of Merkel cell carcinoma, with a focus on immunotherapy and a landscape of future treatment strategies.

Highlights

The history of Merkel cell carcinoma (MCC) therapy is studied with frustration and poor outcomes to treatments until the introduction of immunotherapy, which has radically changed the therapeutic paradigm of this disease.The incidence of MCC is slowly but steadily growing worldwide
PDL1 expression did not correlate with response and just a trend toward improved OS and progression-free survival (PFS) in patients with programmed death-ligand 1 (PD-L1) positivity greater than a 1% threshold on tumor cells was observed, but this did not reach statistical significance
N, number of patients enrolled; Ref, reference; m, median; PFS, progression-free survival; OS, overall survival; ORR, overall response rate; CR, complete response; PR, partial response; SD, stable disease; DCR, disease control rate; DLT, dose-limiting toxicity; MTD, maximum dose tolerated. **If no results are available, we indicate the primary objectives of the study

Summary

INTRODUCTION

The history of Merkel cell carcinoma (MCC) therapy is studied with frustration and poor outcomes to treatments until the introduction of immunotherapy, which has radically changed the therapeutic paradigm of this disease. Increasing knowledge of pathogenesis of MCC has highlighted that both virus-induced MCC and UV-induced MCC had the biological rationale to respond to immunotherapy: in the first case, due to the infectious process (Figure 1), the production of oncoproteins, and the development of an active immune response; in the second case, due to the presence of a very high mutational burden On this wave, and with high expectations, trials with immunotherapy in patients affected by MCC have begun to be conducted with the approval of three different agents, two PD-1 inhibitors and one PD-L1 inhibitor. ORR, overall response rate; mPFS, median progression-free survival: 5-y, 5 years; mOS, median overall survival; I L, first line; II L, second line

62 I line 30 II line

Ipilimumab

III–IV Indium In 111 pentetreotide

Findings

DISCUSSION