To better understand the risks of neurologic toxicities associated with immune checkpoint inhibitors (ICIs).

Case reports have described various neurological immune-related adverse events (irAEs). There still exists a dearth of data regarding their incidence and prognosis.

A single center retrospective study analyzing patients between ages of 18-85 years old from the dates of 3/1/2011 to 9/30/2018 who received immunotherapy for conditions including urothelial cancer, lung cancer, gastric and colorectal cancer, head and neck cancer, lymphoma, melanoma, and renal cell carcinoma.

Of the 1914 subjects who received immunotherapy, 276 experienced neurotoxicity from multiple causes. Of those 276 subjects, 11 suffered neurological irAEs directly from ICI use. Of the 940 subjects who received pembrolizumab alone, 4 (0.004%) developed neurotoxicity 165 to 575 days from administration. Of the 534 subjects who received nivolumab alone, 3 (0.00956%) developed neurotoxicity 477 days from administration. Of the 594 subjects who received ipilimumab alone, 1 (0.0016%) developed neurotoxicity 27 days from administration. Of the 101 subjects who received nivolumab and ipilimumab, 1 (0.0099%) developed neurotoxicity 65 days from administration. Of the 140 subjects who received pembrolizumab and ipilimumab, 2 (0.014%) developed neurotoxicity 240 to 343 days from administration. Ninety-two subjects received atezolizumab, 7 received avelumab, and 18 received durvalumab; none of these patients experienced neurological irAEs. The neurological irAEs observed were neuropathy (45.45%), acute inflammatory demyelinating polyneuropathy (9.09%), ataxia (9.09%), seizure disorder (18.18%), autoimmune encephalitis (18.18%), receptive aphasia (9.09%) and myopathy (9.09%). Neurological irAEs were treated with steroids, intravenous immunoglobulin, and symptomatic medications like gabapentin, duloxetine, levetiracetam, and thiamine, with about 36% of subjects achieving symptom control.

Neurological irAEs were extremely rare in our clinical population, but may correlate to the ICI used. We need larger studies to determine the most effective therapy for each neurological irAE and allow oncologists to recognize and treat them expeditiously.