High-dose interleukin-2: is it still indicated for melanoma and RCC in an era of targeted therapies?

Immunotherapy with interleukin-2 (IL-2) has been the mainstay of systemic therapy for advanced kidney cancer and melanoma. Although IL-2 treatment is limited to healthy patients, a select group of these patients have derived substantial, durable benefit from it-in some translating into cures with no ongoing therapy or chronic toxicity. Over the past 10 years, insights into the biology of renal cell carcinoma and into key signaling mechanisms in melanoma, and growth in our understanding of immune checkpoints, have led to the development and approval of targeted and immune-modulatory therapeutic options with clinically relevant benefit. Our improved understanding of the relationship between the host environment, immune system, and malignancy has helped identify compounds and therapies that are changing the way we think about cancer and our approach to cancer therapeutics. While the newer options may be applicable to most patients, durable responses measured in years are rare. In this review, we examine the currently approved options available for these disease processes, including the newer agents and selected combinatorial approaches under investigation, and we attempt to identify the role of high-dose IL-2 in the context of current clinical practice.