Immune Checkpoint Blockade in Patients With Melanoma Metastatic to the Brain

Metastatic disease to the brain is a frequent manifestation of melanoma and is associated with a very poor outcome. Systemic therapy with cytotoxic chemotherapy provide only a minimal benefit, while surgery and radiotherapy provide in some patients local control but they less frequently affect the overall outcome of melanoma brain metastases (MBM). The advent of active systemic drugs has revolutioned the care of metastatic melanoma, but this benefit has not been translated into intracranial activity. However, since 2010 the anti-CTLA-4 antibody ipilimumab and the BRAF inhibitors, dabrafenib and vemurafenib, have demonstrated initial signs of efficacy in active brain metastases. This chapter reviews the available data and rationale for ongoing and future trials of immune checkpoint-based combination therapy.