Clinical characterization and outcome of 47 patients with neurologic adverse events of immune-checkpoint inhibitors
Elianet Fonseca1, Jose Maria Cabrera Maqueda1, Raquel Ruiz-Garcia1, Laura Naranjo1, Yolanda Blanco Morgado1, Josep Dalmau1, Francesc Graus1, Eugenia Martinez-Hernandez1
1Center of Neuroimmunology, Service of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Universitat de Barcelona
Objective:
To report the clinical spectrum, treatment, and outcome of a case series of neurologic iAEs.
Background:

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


Design/Methods:

 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. 


Results:

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).


Conclusions:

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. 


10.1212/WNL.0000000000203001