Intralesional Oncolytic Versus Systemic Immunotherapy for Advanced Metastatic Melanoma

ABSTRACT Purpose: The purpose of this article is to review the intralesional oncolytic versus systemic immunotherapy patient outcomes for advanced metastatic melanoma and attempt to inform treatment guidelines for this unique population. Method: A PubMed literature search was conducted with search terms advanced metastatic melanoma, oncolytic intralesional therapy, and systematic immunotherapy. Fifty-six pertinent articles were retrieved and serve as the basis for this clinical review. Results: A combination of intralesional treatment modalities and systemically-administered immunomodulatory agents have been proposed as a promising avenue for the treatment of metastatic melanoma. Conclusion: Tumor immunotherapy is becoming an appealing strategy among different therapeutic options of unresectable and metastatic melanoma. Several clinical trials demonstrated the efficacy and tolerable toxicity of systemic immunotherapy by Ipilimumab, CTLA-4 inhibitor, and anti-programmed death receptor-1 antibodies, Nivolumab and Pembrolizumab, in patients with advanced melanoma. The combination of Ipilimumab with Nivolumab marked the beginning of a new era for melanoma immunotherapy. Whereas, nivolumab and pembrolizumab show more preferable safety profile than ipilimumab, and greater efficacy and improved prognosis in melanoma patients. The unique intralesional oncolytic therapy with Talimogene laherparepvec that genetically modified to target tumor cells, and boost the antineoplastic immune response through release of tumor-derived antigens (TDA) and granulocyte-macrophage colony-stimulating factor (GM-CSF), significantly improved the treatment-related grade IIIB/IIIC/IVA of advanced melanoma. Further clinical analysis of combinative immunotherapy is needed to determine the safety, tolerability, and efficacy for patients with regional or distant metastatic melanoma, especially accompanied by the visceral disease that cannot be adequately addressed by surgery. Keywords: T-VEC (Talimogene laherparepvec), Ipilimumab, Pembrolizumab, Nivolumab, Intralesional Oncolytic Therapy, Systematic Immunotherapy, Advanced Metastatic Melanoma