ArticleJournal for immunotherapy of cancer2026
Immune checkpoint inhibitor neurotoxicity: long-term outcomes with focus on 1-year neurological sequelae.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.
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1 citing paper in PubMed, 1 synthesis or guideline pooled it.
- Clinical characteristics, management and outcomes in immune checkpoint inhibitor-induced central nervous system demyelinating disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
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14 authors.
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Abstract
backgroundData on the long-term course of neurological immune-related adverse events (n-irAEs) are limited by the size of studies as well as short and heterogeneous follow-up durations. Herein, we assessed the risk and predictors of 1-year neurological sequelae, and the frequency of n-irAE relapses with or without immune checkpoint inhibitor (ICI) rechallenge.
methodsPatients with Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2 n-irAEs identified in a national reference center were included (2015-2024). Early neurological recovery was defined as CTCAE grade <3 and an improvement of ≥1 point from baseline at 3 months. Long-term sequelae were defined as CTCAE grade ≥2 at 1 year. Associations between prognostic factors and 1-year neurological sequelae were assessed using multivariable logistic regression.
resultsA total of 164 patients were included (median age 69 years, 63% male, median (IQR) follow-up 13 (4-25) months), of whom 59 (36%) had paraneoplastic phenotypes, and 141 (86%) had CTCAE grade 3 or 4 n-irAE at baseline. Most patients (151/163, 93%) received first-line treatments, and 33/163 patients (20%) also received second-line treatments. Early neurological recovery was observed in 82/164 patients (50%). Among 83 patients still alive at 1 year, 33 (40%) had neurological sequelae, and 35 (42%) were receiving treatments. Improvement in CTCAE grade occurred in 13/83 patients (16%) between 3 and 12 months, 1/43 patients (2%) between 12 and 24 months, and it never occurred (0/23) between 24 and 36 months. N-irAE relapses occurred in 25/164 patients (15%), a median (IQR) of 6.8 (3.9-11.8) months after onset. ICI rechallenge led to relapse (CTCAE grade 2) in 1/21 patients (5%). In multivariable analysis, the probability of 1-year neurological sequelae was higher in patients with paraneoplastic phenotypes (OR 11.09, 95% CI (3.24 to 44.51)) and in those who had a relapse within 9 months from baseline (OR 11.12, 95% CI (2.13 to 89.53)). DISCUSSION: Paraneoplastic phenotypes and relapses increase the risk of neurological sequelae among long-term n-irAE survivors, and ICI rechallenge might be safe in n-irAE patients who have fully recovered. The rarity of recovery and low risk of relapse after 1 year suggest that prolonged immunosuppression may be unnecessary, but prospective studies are needed to refine management strategies.
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