Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial.

Autor:	Teulings HE; Dept. of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Depts. of Dermatology, Antoni van Leeuwenhoek Netherlands Cancer Institute, Amsterdam, The Netherlands., Tjin EPM; Dept. of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Willemsen KJ; Dept. of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., van der Kleij S; Depts. of Dermatology, Antoni van Leeuwenhoek Netherlands Cancer Institute, Amsterdam, The Netherlands., Ter Meulen S; Surgical Oncology, Antoni van Leeuwenhoek Netherlands Cancer Institute, Amsterdam, The Netherlands., Kemp EH; Dept. of Oncology and Metabolism, University of Sheffield, Sheffield, UK., Krebbers G; Dept. of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., van Noesel CJM; Dept. of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Franken CLMC; Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands., Drijfhout JW; Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands., Melief CJM; ISA Pharmaceuticals, Leiden, The Netherlands., Nieuweboer-Krobotova L; Dept. of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Depts. of Dermatology, Antoni van Leeuwenhoek Netherlands Cancer Institute, Amsterdam, The Netherlands., Nieweg OE; Surgical Oncology, Antoni van Leeuwenhoek Netherlands Cancer Institute, Amsterdam, The Netherlands., van der Hage JA; Surgical Oncology, Antoni van Leeuwenhoek Netherlands Cancer Institute, Amsterdam, The Netherlands., van der Veen JPW; Dept. of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Depts. of Dermatology, Antoni van Leeuwenhoek Netherlands Cancer Institute, Amsterdam, The Netherlands., Relyveld GN; Depts. of Dermatology, Antoni van Leeuwenhoek Netherlands Cancer Institute, Amsterdam, The Netherlands., Luiten RM; Dept. of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2018 Jan 15; Vol. 7 (4), pp. e1419113. Date of Electronic Publication: 2018 Jan 15 (Print Publication: 2018).
DOI:	10.1080/2162402X.2017.1419113
Abstrakt:	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.
Databáze:	MEDLINE
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