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Case Report: Exceptional Response to Avelumab After Failure of Electrochemotherapy in a Patient With Rapidly Progressive, PD-L1-Negative Merkel Cell Carcinoma

This case report shows, for the first time, a patient experiencing a complete response after one dose of avelumab following extensive disease progression with prior electrochemotherapy (ECT) treatment. We suggest that ECT may help to establish a tumor microenvironment favorable to immunotherapy. Mer...

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Autores principales: Torchio, Martina, Cattaneo, Laura, Milione, Massimo, Prinzi, Natalie, Corti, Francesca, Ungari, Marco, Anichini, Andrea, Mortarini, Roberta, Occhini, Antonio, Bertino, Giulia, Maurichi, Andrea, Coppa, Jorgelina, Di Bartolomeo, Maria, de Braud, Filippo Guglielmo, Pusceddu, Sara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248546/
https://www.ncbi.nlm.nih.gov/pubmed/34221958
http://dx.doi.org/10.3389/fonc.2021.628324
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author Torchio, Martina
Cattaneo, Laura
Milione, Massimo
Prinzi, Natalie
Corti, Francesca
Ungari, Marco
Anichini, Andrea
Mortarini, Roberta
Occhini, Antonio
Bertino, Giulia
Maurichi, Andrea
Coppa, Jorgelina
Di Bartolomeo, Maria
de Braud, Filippo Guglielmo
Pusceddu, Sara
author_facet Torchio, Martina
Cattaneo, Laura
Milione, Massimo
Prinzi, Natalie
Corti, Francesca
Ungari, Marco
Anichini, Andrea
Mortarini, Roberta
Occhini, Antonio
Bertino, Giulia
Maurichi, Andrea
Coppa, Jorgelina
Di Bartolomeo, Maria
de Braud, Filippo Guglielmo
Pusceddu, Sara
author_sort Torchio, Martina
collection PubMed
description This case report shows, for the first time, a patient experiencing a complete response after one dose of avelumab following extensive disease progression with prior electrochemotherapy (ECT) treatment. We suggest that ECT may help to establish a tumor microenvironment favorable to immunotherapy. Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with seldom durable chemotherapy responses. ECT has recently emerged as a potential treatment option for several malignancies, including MCC. Avelumab, an anti-programmed cell death-ligand 1 (PD-L1) monoclonal antibody, became the first approved treatment for patients with metastatic MCC. ECT has been shown to activate the immune response, but it is still unknown how ECT may affect patient’s response to subsequent immunotherapy. We report a case of a patient with MCC who presented with a rapidly growing skin nodule of the right cheek and experienced extensive disease progression following surgical debulking and ECT treatment. The patient received a flat dose of 800 mg avelumab intravenously every 2 weeks showing complete tumor regression after only one dose. Immunohistochemical analysis of surgical and post-ECT biopsies collected from the primary lesion revealed tumor expression of programmed cell death protein-1 (PD-1), but not PD-L1. Analysis of the tumor samples also revealed no expression of Merkel cell polyomavirus (MCPyV). Comparison of the biopsies showed a decrease in myeloid and T-cell markers after ECT but an increase in major histocompatibility complex (MHC) class I expression on tumor cells. Additionally, the patient experienced an increase in neutrophil-to-lymphocyte ratio and lactate dehydrogenase values post-ECT, which subsequently decreased with avelumab treatment. As of 30 October 2019, the patient was still receiving avelumab treatment and had an ongoing complete response. In this case report, a patient with PD-L1-negative and MCPyV-negative MCC who had disease progression following ECT experienced complete tumor regression with avelumab treatment, suggesting, for the first time to our knowledge, that ECT may help to establish a tumor microenvironment favorable to immunotherapy via a potential abscopal effect. Tumor-intrinsic PD-1 expression and modulation of MHC class I antigens after ECT may contribute to the clinical efficacy of avelumab in this context.
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spelling pubmed-82485462021-07-02 Case Report: Exceptional Response to Avelumab After Failure of Electrochemotherapy in a Patient With Rapidly Progressive, PD-L1-Negative Merkel Cell Carcinoma Torchio, Martina Cattaneo, Laura Milione, Massimo Prinzi, Natalie Corti, Francesca Ungari, Marco Anichini, Andrea Mortarini, Roberta Occhini, Antonio Bertino, Giulia Maurichi, Andrea Coppa, Jorgelina Di Bartolomeo, Maria de Braud, Filippo Guglielmo Pusceddu, Sara Front Oncol Oncology This case report shows, for the first time, a patient experiencing a complete response after one dose of avelumab following extensive disease progression with prior electrochemotherapy (ECT) treatment. We suggest that ECT may help to establish a tumor microenvironment favorable to immunotherapy. Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with seldom durable chemotherapy responses. ECT has recently emerged as a potential treatment option for several malignancies, including MCC. Avelumab, an anti-programmed cell death-ligand 1 (PD-L1) monoclonal antibody, became the first approved treatment for patients with metastatic MCC. ECT has been shown to activate the immune response, but it is still unknown how ECT may affect patient’s response to subsequent immunotherapy. We report a case of a patient with MCC who presented with a rapidly growing skin nodule of the right cheek and experienced extensive disease progression following surgical debulking and ECT treatment. The patient received a flat dose of 800 mg avelumab intravenously every 2 weeks showing complete tumor regression after only one dose. Immunohistochemical analysis of surgical and post-ECT biopsies collected from the primary lesion revealed tumor expression of programmed cell death protein-1 (PD-1), but not PD-L1. Analysis of the tumor samples also revealed no expression of Merkel cell polyomavirus (MCPyV). Comparison of the biopsies showed a decrease in myeloid and T-cell markers after ECT but an increase in major histocompatibility complex (MHC) class I expression on tumor cells. Additionally, the patient experienced an increase in neutrophil-to-lymphocyte ratio and lactate dehydrogenase values post-ECT, which subsequently decreased with avelumab treatment. As of 30 October 2019, the patient was still receiving avelumab treatment and had an ongoing complete response. In this case report, a patient with PD-L1-negative and MCPyV-negative MCC who had disease progression following ECT experienced complete tumor regression with avelumab treatment, suggesting, for the first time to our knowledge, that ECT may help to establish a tumor microenvironment favorable to immunotherapy via a potential abscopal effect. Tumor-intrinsic PD-1 expression and modulation of MHC class I antigens after ECT may contribute to the clinical efficacy of avelumab in this context. Frontiers Media S.A. 2021-06-17 /pmc/articles/PMC8248546/ /pubmed/34221958 http://dx.doi.org/10.3389/fonc.2021.628324 Text en Copyright © 2021 Torchio, Cattaneo, Milione, Prinzi, Corti, Ungari, Anichini, Mortarini, Occhini, Bertino, Maurichi, Coppa, Di Bartolomeo, de Braud and Pusceddu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Torchio, Martina
Cattaneo, Laura
Milione, Massimo
Prinzi, Natalie
Corti, Francesca
Ungari, Marco
Anichini, Andrea
Mortarini, Roberta
Occhini, Antonio
Bertino, Giulia
Maurichi, Andrea
Coppa, Jorgelina
Di Bartolomeo, Maria
de Braud, Filippo Guglielmo
Pusceddu, Sara
Case Report: Exceptional Response to Avelumab After Failure of Electrochemotherapy in a Patient With Rapidly Progressive, PD-L1-Negative Merkel Cell Carcinoma
title Case Report: Exceptional Response to Avelumab After Failure of Electrochemotherapy in a Patient With Rapidly Progressive, PD-L1-Negative Merkel Cell Carcinoma
title_full Case Report: Exceptional Response to Avelumab After Failure of Electrochemotherapy in a Patient With Rapidly Progressive, PD-L1-Negative Merkel Cell Carcinoma
title_fullStr Case Report: Exceptional Response to Avelumab After Failure of Electrochemotherapy in a Patient With Rapidly Progressive, PD-L1-Negative Merkel Cell Carcinoma
title_full_unstemmed Case Report: Exceptional Response to Avelumab After Failure of Electrochemotherapy in a Patient With Rapidly Progressive, PD-L1-Negative Merkel Cell Carcinoma
title_short Case Report: Exceptional Response to Avelumab After Failure of Electrochemotherapy in a Patient With Rapidly Progressive, PD-L1-Negative Merkel Cell Carcinoma
title_sort case report: exceptional response to avelumab after failure of electrochemotherapy in a patient with rapidly progressive, pd-l1-negative merkel cell carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248546/
https://www.ncbi.nlm.nih.gov/pubmed/34221958
http://dx.doi.org/10.3389/fonc.2021.628324
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