Cancer treatment with immune checkpoint inhibitors (ICI) can associate with immune-related adverse events (iAEs) which can be life-threatening.

 Retrospective assessment of patients with neurologic iAEs whose serum or CSF samples were studied in our laboratory (Jan2018-Sep2022). Clinical information was obtained through a structured questionnaire. Exclusion criteria were lack of clinical information and evidence of other causes of neurologic dysfunction. Treatment response was assessed within one month of symptom onset, and outcome at last follow-up visit. 

47 patients (29 males, 62%), median age 67 years (IQR60-74) were included. The most frequent tumors were lung cancer (28, 60%) and melanoma (9, 19%). 26 (55%) patients received anti-PD1, 13 (28%) PDL-1, and 8 (17%) both. Median time to neurologic iAEs was 15 weeks (IQR3-32). The initial presentations were:  encephalopathy  (30 patients, 64%), muscle weakness  (9, 19%), ataxia  (3, 6%), visual dysfunction  (3, 6%), and constipation  (2, 4%). Median mRS at nadir was 4 (3-5), and 7 (15%) patients required ICU. Abs were detected in 10 (21%; Ma2=3, Hu=2, GFAP=2, GABAbR=1, GAD65=1, AQP4=1). 42 (89%) were treated; all received steroids, 17 (36%) intravenous immunoglobulins, and 9 (21%) other immunosuppressants. Patients without early neurologic improvement (14, 30%) were more likely to be older, have lung cancer (p=0.01), and higher mRS at nadir (p=0.001) than those who improved. After a median follow-up of 107 days (45-356), mRS was 3 (0-6), and 26 (55%) patients had a poor outcome: 23 (49%) died (10 [21%] related to neurologic iAE) and the other 3 didn’t improve or worsened. Good outcome was associated with early neurologic improvement (p=0.001).

In this case series with predominant CNS iAEs, half of the patients had poor clinical outcome, and in 20% the neurologic iAE was the cause of death.