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

OncoImmunology

Gabrielle Krebbers¹  Carel J. M. van Noesel¹  Rosalie M. Luiten¹  Karina J. Willemsen¹  Esther P. M. Tjin¹  J. P. Wietze van der Veen¹  Hansje-Eva Teulings¹  Ludmila Nieuweboer-Krobotova¹  Stephanie van der Kleij²  Germaine N. Relyveld²  Cornelis J. M. Melief³  Jan W. Drijfhout⁴  Cornelis L. M. C. Franken⁴  Omgo E. Nieweg⁵  Jos A. van der Hage⁵  Sylvia ter Meulen⁵  E. Helen Kemp⁶ 

[1] Academic Medical Center, University of Amsterdam;Antoni van Leeuwenhoek Netherlands Cancer Institute;ISA Pharmaceuticals;Leiden University Medical Center;Surgical Oncology, Antoni van Leeuwenhoek Netherlands Cancer Institute;University of Sheffield;

关键词: melanoma;    immunotherapy;    vitiligo;    cutaneous metastases;   

DOI  :  10.1080/2162402X.2017.1419113

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown