High-dose interleukin-2 (IL-2) for the treatment of melanoma: safety considerations and future directions

Expert Opin Drug Saf. 2017 Dec;16(12):1347-1357. doi: 10.1080/14740338.2017.1382472. Epub 2017 Sep 21.


In 1998, high-dose interleukin-2 (IL-2) was the first immunotherapy approved for the treatment of metastatic melanoma based on durable objective responses documented in a subset of patients but widespread utilization was limited by significant toxicity. Advances in targeted therapy and the emergence of T cell checkpoint inhibitors, which can generally be given in the ambulatory setting, have further limited consideration of IL-2 for melanoma patients and the role of IL-2 in the current landscape of melanoma treatment is uncertain. Areas covered: In this review, we will describe advances in clinical diagnostic and management strategies that have improved the therapeutic window for IL-2 therapy in patients with melanoma. Further, we will describe the potential for using IL-2 in patients whose disease has progressed after other interventions or as part of combination immunotherapy approaches that are now in clinical development. We will also review the common toxicities of IL-2 therapy and their current management will be discussed. Expert opinion: High-dose IL-2 remains an important option for patients with melanoma and has an improved therapeutic window in the contemporary era. The reasons why IL-2 is not utilized more frequently and measures for enhancing its use will be detailed.

Keywords: Immunotherapy; interleukin-2; melanoma; safety.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / adverse effects
  • Interleukin-2 / therapeutic use*
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Neoplasm Metastasis
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology


  • Antineoplastic Agents
  • Interleukin-2