Late-onset Neurological Immune-related Adverse Events Associated with Immune Checkpoint Inhibitors
Naga Pradyumna Kothapalli1, Nihar Upadhyay1, Lisa Kottschade1, Teerin Liewluck2, Anastasia Zekeridou3, Divyanshu Dubey1
1Mayo Clinic, 2Department of Neurology, Mayo Clinic, 3Neuroimmunology Laboratory, Mayo Clinic
Objective:

To evaluate the late-onset adverse events in a large cohort to better characterize their clinical phenotypes and outcomes.

Background:
Immune related adverse events
Design/Methods:
Retrospective study included patients with late-onset N-irAE, defined as onset ≥ 6 months after ICI initiation. Mayo Clinic patients (2016-2025) underwent extensive testing to rule out mimics. We compared cohorts with intermediate N-irAE onset (1-6 months after ICI initiation), early onset (≤1 month after ICI initiation), performed a time-to-death analysis.
Results:

95 N-irAEs, 35 (37%) were late-onset, median age at onset of 66 years (vs 71 in early-onset, P<0.05), female 64% (versus 38% in early-onset, P<0.05). In late-onset N-irAE, 50% of patients had prior radiation and chemotherapy before initiating ICI, compared with 79% in early-onset cases (P<0.05). Median time from cancer diagnosis to ICI initiation was 12 months (IQR 2–48), longer than in early-onset N-irAEs (4 months, IQR 2–31; P<0.05) and intermediate-onset N-irAEs (2 months, IQR 1–8; P<0.05). Eight patients switched ICI classes during treatment (none in the early or intermediate-onset groups; P<0.05). Myopathy was present in 17% of late-onset cases (versus 75% in early-onset, P<0.05); 20% had other peripheral neurological manifestations (vs 3% in early-onset, P<0.05); 14% experienced paraneoplastic neurological syndromes (vs none in early-onset, P<0.05); 6% had fulminant course (vs 30% in early-onset, P<0.05). Nine patients had CNS manifestations other than autoimmune encephalitis/meningitis in late onset (vs 3 each in early/intermediate onset, P<0.05). Mortality from N-irAE was higher in early-onset cases, from myopathy (P<0.05). Deaths from cancer progression were more in late-onset cases, this difference was not statistically significant, due to small sample size. Antibodies in late-onset cohort ANNA-1 (n = 3, one with coexisting NIF), 1 each GAD-65 and AQP4. Intermediate-onset cohort included one each CRMP-5, P/Q channel. 

Conclusions:

Late-onset N-irAEs are common, should be recognized with appropriate testing, associated with favorable outcomes compared to early-onset N-irAEs. 

Generative AI Usage
No, did not use generative AI in the drafting or editing in this abstract.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.