Immune Checkpoint Inhibitor Associated Central Nervous System Autoimmunity.

Abstract

Outcome and re-challenge data of central nervous system (CNS) autoimmunity triggered by immune checkpoint inhibitors (ICI) are limited. We aim to describe a large series of ICI-triggered CNS-autoimmunity, and to compare these patients with spontaneous paraneoplastic syndromes (PNS). Retrospective review of Mayo Clinic patients with ICI-triggered CNS-autoimmunity (2/2015-6/2021). Clinical characteristics were compared to spontaneous PNS patients (with antineuronal nuclear antibody [ANNA]-1 or (anti-Hu) and/or neuroendocrine tumors [NET] within the same period. Thirty-one patients were included, 55% female, median age 63 years (range 39-76). Median time from ICI initiation was 3.65 months (range 0.8-44.5). Most common associated malignancies were melanoma and small-cell lung cancer. CNS manifestations included encephalitis (16), meningoencephalitis (8), cerebellar ataxia (4), demyelinating syndrome (2), myelopathy (1). MRI was abnormal in 62%. CSF was inflammatory in 70%. Neural autoantibodies were identified in 47%, more frequently in patients with NET (P=0.046). ICI was discontinued in 97%; 90% received immunosuppressive treatment. After median 6.8 months follow-up (range 0.7-46), 39% had unfavorable outcomes (grade ≥3). This associated with higher severity degree at onset, shorter period from ICI to neurological onset, and encephalitis. Four patients were re-challenged with ICI and one relapsed. Patients with NET and with ANNA-1 ICI-triggered CNS autoimmunity had associated peripheral nervous system manifestations more frequently than their spontaneous counterparts (P=0.007 and P=0.028, respectively). One third of ICI-related CNS-autoimmunity patients have unfavorable outcomes related to their clinical presentation. Relapses may occur after ICI re-challenge. Neural autoantibodies are often present, more commonly in patients with NET.