Alessandro Marini1, Andrea Bernardini1, Gian Luigi Gigli1, Mariarosaria Valente1, Sergio Muñiz-Castrillo1, Jérôme Honnorat1, Alberto Vogrig2. 1. From the Clinical Neurology Unit (A.M., A.B., G.L.G., M.V., A.V.), Santa Maria Della Misericordia University Hospital; Department of Medicine (DAME) (A.M., G.L.G., M.V.), University of Udine Medical School, Italy; French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (S.M.-C., J.H., A.V.), Hospices Civils de Lyon, Hôpital Neurologique; Synatac Team (S.M.-C., J.H., A.V.), NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310; and University Claude Bernard Lyon 1 (S.M.-C., J.H., A.V.), Université de Lyon, France. 2. From the Clinical Neurology Unit (A.M., A.B., G.L.G., M.V., A.V.), Santa Maria Della Misericordia University Hospital; Department of Medicine (DAME) (A.M., G.L.G., M.V.), University of Udine Medical School, Italy; French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (S.M.-C., J.H., A.V.), Hospices Civils de Lyon, Hôpital Neurologique; Synatac Team (S.M.-C., J.H., A.V.), NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310; and University Claude Bernard Lyon 1 (S.M.-C., J.H., A.V.), Université de Lyon, France. alberto.vogrig@gmail.com.
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.
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.