Melanoma Brain Metastases: Unique Biology and Implications for Systemic Therapy

Melanoma has a very high propensity to metastasize to the central nervous system (CNS), including the brain and leptomeninges. Neurosurgery and stereotactic radiosurgery represent valuable and effective modalities and have been the mainstay of therapy for melanoma metastatic to the brain. Integration of these modalities with systemic therapy in a multidisciplinary approach is critical for the management of this complex and devastating complication of metastatic melanoma. Advances in systemic therapy recently led to clinical benefit for patients with melanoma brain metastases (MBM), with high response rates observed for combination targeted therapies and combination immune checkpoint locking antibodies. However, the duration of response seems to be more limited for targeted therapy than for the durable responses induced by immunotherapy. The underlying biological tenets of response and resistance to targeted and immune therapies are thoroughly discussed in this chapter. We also review the challenges of measuring clinical benefit andoffer a perspective for future drug development in this unique patient population.