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Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial
Vitiligo development in melanoma patients during immunotherapy is a favorable prognostic sign and indicates breakage of tolerance against melanocytic/melanoma antigens. We investigated a novel immunotherapeutic approach of the skin-depigmenting compound monobenzone synergizing with imiquimod in indu...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889200/ https://www.ncbi.nlm.nih.gov/pubmed/29632737 http://dx.doi.org/10.1080/2162402X.2017.1419113 |
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author | Teulings, Hansje-Eva Tjin, Esther P. M. Willemsen, Karina J. van der Kleij, Stephanie ter Meulen, Sylvia Kemp, E. Helen Krebbers, Gabrielle van Noesel, Carel J. M. Franken, Cornelis L. M. C. Drijfhout, Jan W. Melief, Cornelis J. M. Nieuweboer-Krobotova, Ludmila Nieweg, Omgo E. van der Hage, Jos A. van der Veen, J. P. Wietze Relyveld, Germaine N. Luiten, Rosalie M. |
author_facet | Teulings, Hansje-Eva Tjin, Esther P. M. Willemsen, Karina J. van der Kleij, Stephanie ter Meulen, Sylvia Kemp, E. Helen Krebbers, Gabrielle van Noesel, Carel J. M. Franken, Cornelis L. M. C. Drijfhout, Jan W. Melief, Cornelis J. M. Nieuweboer-Krobotova, Ludmila Nieweg, Omgo E. van der Hage, Jos A. van der Veen, J. P. Wietze Relyveld, Germaine N. Luiten, Rosalie M. |
author_sort | Teulings, Hansje-Eva |
collection | PubMed |
description | Vitiligo development in melanoma patients during immunotherapy is a favorable prognostic sign and indicates breakage of tolerance against melanocytic/melanoma antigens. We investigated a novel immunotherapeutic approach of the skin-depigmenting compound monobenzone synergizing with imiquimod in inducing antimelanoma immunity and melanoma regression. Stage III-IV melanoma patients with non-resectable cutaneous melanoma metastases were treated with monobenzone and imiquimod (MI) therapy applied locally to cutaneous metastases and adjacent skin during 12 weeks, or longer. Twenty-one of 25 enrolled patients were evaluable for clinical assessment at 12 weeks. MI therapy was well-tolerated. Partial regression of cutaneous metastases was observed in 8 patients and stable disease in 1 patient, reaching the statistical endpoint of treatment efficacy. Continued treatment induced clinical response in 11 patients, including complete responses in three patients. Seven patients developed vitiligo-like depigmentation on areas of skin that were not treated with MI therapy, indicating a systemic effect of MI therapy. Melanoma-specific antibody responses were induced in 7 of 17 patients tested and melanoma-specific CD8+T-cell responses in 11 of 15 patients tested. These systemic immune responses were significantly increased during therapy as compared to baseline in responding patients. This study shows that MI therapy induces local and systemic anti-melanoma immunity and local regression of cutaneous metastases in 38% of patients, or 52% during prolonged therapy. This study provides proof-of-concept of MI therapy, a low-cost, broadly applicable and well-tolerated treatment for cutaneous melanoma metastases, attractive for further clinical investigation. |
format | Online Article Text |
id | pubmed-5889200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-58892002018-04-09 Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial Teulings, Hansje-Eva Tjin, Esther P. M. Willemsen, Karina J. van der Kleij, Stephanie ter Meulen, Sylvia Kemp, E. Helen Krebbers, Gabrielle van Noesel, Carel J. M. Franken, Cornelis L. M. C. Drijfhout, Jan W. Melief, Cornelis J. M. Nieuweboer-Krobotova, Ludmila Nieweg, Omgo E. van der Hage, Jos A. van der Veen, J. P. Wietze Relyveld, Germaine N. Luiten, Rosalie M. Oncoimmunology Original Research Vitiligo development in melanoma patients during immunotherapy is a favorable prognostic sign and indicates breakage of tolerance against melanocytic/melanoma antigens. We investigated a novel immunotherapeutic approach of the skin-depigmenting compound monobenzone synergizing with imiquimod in inducing antimelanoma immunity and melanoma regression. Stage III-IV melanoma patients with non-resectable cutaneous melanoma metastases were treated with monobenzone and imiquimod (MI) therapy applied locally to cutaneous metastases and adjacent skin during 12 weeks, or longer. Twenty-one of 25 enrolled patients were evaluable for clinical assessment at 12 weeks. MI therapy was well-tolerated. Partial regression of cutaneous metastases was observed in 8 patients and stable disease in 1 patient, reaching the statistical endpoint of treatment efficacy. Continued treatment induced clinical response in 11 patients, including complete responses in three patients. Seven patients developed vitiligo-like depigmentation on areas of skin that were not treated with MI therapy, indicating a systemic effect of MI therapy. Melanoma-specific antibody responses were induced in 7 of 17 patients tested and melanoma-specific CD8+T-cell responses in 11 of 15 patients tested. These systemic immune responses were significantly increased during therapy as compared to baseline in responding patients. This study shows that MI therapy induces local and systemic anti-melanoma immunity and local regression of cutaneous metastases in 38% of patients, or 52% during prolonged therapy. This study provides proof-of-concept of MI therapy, a low-cost, broadly applicable and well-tolerated treatment for cutaneous melanoma metastases, attractive for further clinical investigation. Taylor & Francis 2018-01-15 /pmc/articles/PMC5889200/ /pubmed/29632737 http://dx.doi.org/10.1080/2162402X.2017.1419113 Text en © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Teulings, Hansje-Eva Tjin, Esther P. M. Willemsen, Karina J. van der Kleij, Stephanie ter Meulen, Sylvia Kemp, E. Helen Krebbers, Gabrielle van Noesel, Carel J. M. Franken, Cornelis L. M. C. Drijfhout, Jan W. Melief, Cornelis J. M. Nieuweboer-Krobotova, Ludmila Nieweg, Omgo E. van der Hage, Jos A. van der Veen, J. P. Wietze Relyveld, Germaine N. Luiten, Rosalie M. Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial |
title | Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial |
title_full | Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial |
title_fullStr | Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial |
title_full_unstemmed | Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial |
title_short | Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial |
title_sort | anti-melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889200/ https://www.ncbi.nlm.nih.gov/pubmed/29632737 http://dx.doi.org/10.1080/2162402X.2017.1419113 |
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