CNS demyelination and enhanced myelin-reactive responses after ipilimumab treatment

Ipilimumab is a monoclonal antibody that prolongs survival in patients with metastatic melanoma.(1) It targets the coinhibitory receptor cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 signaling induces a state of T-cell unresponsiveness, which facilitates tumor escape from immune surveillance. Blockade of CTLA-4 is believed to shift the immune status from T-cell exhaustion to a functional antitumor response. Anti-CTLA-4 therapy is associated with immune-related adverse events in 64% of patients. Autoimmunity involving the nervous system has a low incidence and manifests predominantly as peripheral inflammatory neuropathy.(2) We report new-onset inflammatory CNS demyelination in an ipilimumab-treated melanoma patient (figure), confirmed by histology and associated with enhanced responses of myelin-reactive CD4+ T cells.