The management of metastatic melanoma has been transformed by the development of immune checkpoint inhibitors. However, disease control in patients with extensive locoregional metastases remains a significant challenge. In this context, intralesional interleukin 2 (IL-2) presents a useful therapeutic option to maximize intratumoural drug concentration and minimize systemic toxicity. The utility of combined intralesional IL-2 and systemic immune checkpoint therapy, particularly in loco-regional disease, is unknown. We report the clinical and cellular effects of combined anti-programmed death-1 blockade and intralesional IL-2 therapy in two patients with loco-regional metastatic melanoma. Combined intralesional and systemic therapy induced a lasting resolution of the injected skin tumors; maintained for up to 2 years. This impressive response was associated with increased PD-L1 expression and CD8 T cell infiltration. To our knowledge, this is the first report that raises the possibility of a synergistic effect between intralesional IL-2 and systemic checkpoint inhibition. The lasting remission of injected metastases may be in part due to an altered tumor microenvironment; characterized by increased PD-L1 expression and increased CD8 T cell infiltration. If this interesting and novel preliminary observation is confirmed in larger studies, combined local and systemic immunotherapy could highlight a novel treatment strategy for extensive loco-regional disease.
Keywords: PD-L1; checkpoint inhibitors; interleukin 2; melanoma.
© 2019 Wiley Periodicals, Inc.