Severe Immune-Related Neurological Adverse Events Associated With Immune Checkpoint Inhibitor Treatment: A Retrospective Single-Center Study

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies. The resulting activation of the immune system may lead to neurological immune-related adverse events (n-irAEs). Here, we retrospectively characterized severe n-irAEs in a monocentric cohort.

Methods: We screened an in-house registry of the Medical University of Vienna, Austria, including all patients treated with ICIs between 2007 and 2023. Patients who underwent a neurological evaluation were identified, and their medical records were reviewed. Cases with severe (i.e., grade ≥ 3) n-irAEs were analyzed. We report clinical and demographic characteristics, neurological manifestations, treatment and outcomes.

Results: Ten out of 2043 screened patients (i.e., 0.5%) developed severe n-irAEs. In most cases (n = 7), neurological manifestations involved the neuromuscular system and/or peripheral nerves, including myasthenia/myositis (n = 5), polyneuropathy (n = 1), and facial nerve palsy (n = 1). Central nervous system involvement included aseptic meningitis, myelitis, and stroke (each n = 1). The number of ICI cycles prior to n-irAE onset varied, with a median of 3 cycles (range 1-43). The median time from the last infusion to symptom onset was 7 days (range 2-24). n-irAEs led to ICI discontinuation and/or immunomodulatory treatments in 9 patients. Clinical improvement was observed in 7 of 10 cases. No deaths were attributed to ICI-related toxicity.

Conclusion: Our findings indicate that severe n-irAEs are rare. Nonetheless, clinicians should remain vigilant for delayed-onset neurotoxicity, even after long treatment exposure. Most patients showed clinical improvement following ICI discontinuation and/or immunomodulatory treatments.

Keywords: PD‐1; PD‐L1; adverse events; immune checkpoint inhibitor; neurological; n‐irAE.