Immune check point inhibitor (ICI) therapies targeting cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), programmed cell death (PD-1) and its ligand PD-L1 used for cancer treatment can cause neurologic immune related adverse events (irAE). 

To characterize the neurological toxicities in cancer patients receiving immune check-point inhibitor therapy.

This is a single-center retrospective analysis of 11 patients who received ICI therapy for cancer at the National Institutes of Health (NIH) with reported neurological irAE (neuro-irAE). Informed consent was obtained. 

Eleven patients were treated with either nivolumab, pembrolizumab, durvalumab, nivolumab+ipilimumab, or nivolumab+CEA-MUC-1-TRICOM vaccine CV301. All patients had metastatic genitourinary cancers or non-small cell lung cancer. The median time to onset of neuro-irAE was 4.4 months (range – 0.5-12).  One patient on nivolumab +ipilimumab combination developed autoimmune limbic encephalitis on MRI with lymphocytic pleocytosis and progressive 6^thcranial nerve palsies. Another patient on nivolumab had aseptic meningitis with mild leptomeningeal enhancement on MRI, lymphocytic pleocytosis and increased protein. One patient on nivolumab+ CV301 developed multifocal embolic infarcts. One patient on durvalumab plus olaparib had optic neuritis. Treatment with immune checkpoint inhibitor was held in five patients and continued in six patients. Using CTCAE v4.03 criteria, all neuro-irAEs were grade 3 or below, with 5/16 grade 3, 8/16 grade 2, and 2/16 grade 1. 13/16 neuro-irAEs were definitely, probably or possibly related to study drug, with only 3/16 events being unlikely to be related to ICI therapy. 

9/11 patients had immune-mediated neurological AEs related to study drug. 7/16 of the neurologic irAEs were definitely related to study drug. In this series, 5/7 definitely related irAEs resulted from combination ICI therapy. In summary, immune check point modulation has the potential to cause a variety of serious autoimmune neurological adverse events.