Neurological complications induced by checkpoint inhibitors: characterising the clinical spectra
Anne Merel van Wylick, Martin van den Bent, Bart C Jacobs, Maarten Titulaer, Jeroen Kerstens, Esther Brusse, Ron H J Mathijssen, Daphne W Dumoulin, Astrid A M van der Veldt, Marjolein GeurtsBackground
Timely recognition of immune checkpoint immune-related neurological adverse events (irNAEs) is critical given their potential severity, yet remains challenging due to limited clinical experience. This study investigates clinical presentation and management of irNAEs from a neurological perspective.
Methods
We retrospectively identified all patients treated with immune checkpoint inhibitors (ICIs) at Erasmus MC Cancer Institute, Rotterdam, The Netherlands between 2017 and 2024. Patient records were analysed by a neurologist for clinical and treatment of irNAE post-ICI initiation.
Results
Of 3176 ICI-treated patients, irNAE was diagnosed in 76 cases (2.4%). Peripheral syndromes occurred in 55 (70%), central in 21 (30%) patients. Classification into distinct disease entities was challenging due to remarkable overlap in affected neurological structures. Median onset of irNAE was 8 weeks after ICI initiation (range 1–104 weeks); 70% developed within 18 weeks. IrNAE-related mortality was 13%, observed only in the first 18 weeks. Fewer non-small cell lung cancer patients developed irNAE (OR, 0.36; 95% CI 0.16 to 0.8; p=0.012) compared with other tumour types. Males (OR, 1.78; 95% CI 1.1 to 2.90; p=0.019) and PD1/CTLA4 combination therapy (OR 2.1, 95% CI 1.28 to 3.46, p=0.004) were associated with increased irNAE incidence. Glucocorticoids were given in 64% of patients; 14% received immunosuppressive therapy beyond steroids. Treatment response varied widely, both clinically and temporally.
Conclusion
This retrospective single-centre study confirms irNAEs are infrequent complications of ICI. The distinct symptom profile, with substantial overlap within affected neurological structures, underscores the need for neurological expertise in irNAE care. While most develop within 18 weeks of treatment, late-onset cases occur. Mortality occurred only in early-onset cases.