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Abstract
Objective To define the clinical characteristics, management, and outcome of neurologic immune-related adverse events (n-irAEs) of immune checkpoint inhibitors (ICIs).
Methods Systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Results A total of 694 articles were identified. Two hundred fifty-six articles, with 428 individual patients, met the inclusion criteria. Reports regarding neuromuscular disorders (319/428, 75%) were more frequent than those on CNS disorders (109/428, 25%). The most common n-irAEs reports were myositis (136/428, 32%), Guillain-Barré syndrome and other peripheral neuropathies (94/428, 22%), myasthenic syndromes (58/428, 14%), encephalitis (56/428, 13%), cranial neuropathies (31/428, 7%), meningitis (13/428, 3%), CNS demyelinating diseases (8/428, 2%), and myelitis (7/428, 2%). Other CNS disorders were detected in 25/428 (6%) patients. Compared with the whole sample, myasthenic syndromes were significantly more Ab positive (33/56, 59%; p < 0.001). Anti–programmed cell death protein 1/programmed cell death ligand 1 was more frequent in myasthenic syndromes (50/58, 86%; p = 0.005) and less common in meningitis (2/13, 15%; p < 0.001) and cranial neuropathies (13/31, 42%; p = 0.005). Anti–cytotoxic T-lymphocyte antigen-4 ICIs were more frequent in meningitis (8/13, 62%; p < 0.001) and less common in encephalitis (2/56, 4%; p = 0.009) and myositis (12/136, 9%; p = 0.01). Combination of different ICIs was more frequent in cranial neuropathies (12/31, 39%; p = 0.005). Melanoma was more frequent in patients with peripheral neuropathies (64/94, 68%; p = 0.003) and less common in encephalitis (19/56, 34%; p = 0.001). The highest mortality rate was reached in myasthenic syndromes (28%).
Conclusion Considering the increasing use of ICI therapy in the forthcoming future, this information can be valuable in assisting neurologists and oncologists in early n-irAEs diagnosis and treatment.
Glossary
- AchR=
- acetylcholine receptor;
- AQP4=
- aquaporin 4;
- CTLA-4=
- cytotoxic T-lymphocyte antigen-4;
- GBS=
- Guillain-Barré syndrome;
- ICI=
- immune checkpoint inhibitor;
- LEMS=
- Lambert-Eaton myasthenic syndrome;
- LETM=
- longitudinally extensive transverse myelitis;
- MG=
- myasthenia gravis;
- MOG=
- myelin oligodendrocyte glycoprotein;
- MusK=
- muscle-specific kinase;
- n-irAE=
- neurologic immune-related adverse event;
- NMOSD=
- neuromyelitis optica spectrum disorder;
- OCB=
- oligoclonal band;
- PD-1=
- programmed cell death protein 1;
- PD-L1=
- programmed cell death ligand 1;
- PRES=
- posterior reversible encephalopathy syndrome
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Data access, responsibility, and analysis: the corresponding author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Editorial, page 733
- Received July 4, 2020.
- Accepted in final form January 28, 2021.
- © 2021 American Academy of Neurology
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