Immune checkpoint inhibitor-associated central nervous system autoimmunity

Area of Science:

• Neuroimmunology
• Oncology
• Neurology

Background:

• Central nervous system (CNS) autoimmunity can be triggered by immune checkpoint inhibitors (ICIs).
• Limited data exists on the outcomes and rechallenge of ICI-induced CNS autoimmunity.
• Comparison with spontaneous paraneoplastic syndromes (PNS) is needed.

Purpose of the Study:

• To describe a large cohort of patients with ICI-triggered CNS autoimmunity.
• To compare ICI-triggered CNS autoimmunity with spontaneous PNS.
• To analyze outcomes and rechallenge data.

Main Methods:

• Retrospective review of Mayo Clinic patients with ICI-triggered CNS autoimmunity (February 2015-June 2021).
• Comparison with spontaneous PNS patients (ANNA-1 or anti-Hu, and/or NET) evaluated during the same period.
• Analysis of clinical characteristics, outcomes, and rechallenge data.

Main Results:

• Thirty-one patients with ICI-triggered CNS autoimmunity were identified (median age 63).
• Common malignancies included melanoma and small cell lung cancer; CNS manifestations varied (encephalitis, meningoencephalitis, ataxia).
• 47% had neural autoantibodies, more frequent in NET patients. 39% experienced unfavorable outcomes, associated with higher severity and shorter time to onset. One relapse occurred after ICI rechallenge.

Conclusions:

• Approximately one-third of patients with ICI-related CNS autoimmunity experience unfavorable outcomes.
• Relapses can occur following ICI rechallenge.
• Neural autoantibodies are frequently detected, especially in patients with neuroendocrine tumors.