Long-Term Outcomes of Immune Checkpoint Inhibition in Metastatic Melanoma

Increasing knowledge about the biology of melanoma and of immunology has led to the development and regulatory approval of the immune checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab, which are indicated for the treatment of melanoma irrespective of the B-Raf proto-oncogene mutation status of the tumour. Only a subset of patients will respond, but those who do can expect long-lasting, previously unheard-of responses. Long-term survival results for the registration trials, including CheckMate 067, Keynote-006, and Keynote-001, have recently been published. In particular, the combination of ipilimumab and nivolumab showed an impressive 5-year overall survival of just over 50%. However, toxicity remains a significant concern, with some of the side effects being life threatening and/or life changing. In this review, we discuss the safety and efficacy data of all the agents currently approved for the first-line treatment of advanced melanoma, identifying factors that influence the choice of a single agent rather than combination therapy. We highlight the potential biomarkers of response, effects of long-term toxicity, and options after progression.