Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study

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dc.contributor.authorFonseca, Elianet
dc.contributor.authorCabrera-Maqueda, Jose M.
dc.contributor.authorRuiz-Garcia, Raquel
dc.contributor.authorNaranjo, Laura
dc.contributor.authorDiaz-Pedroche, Carmen
dc.contributor.authorVelasco, Roser
dc.contributor.authorMacias-Gomez, Adria
dc.contributor.authorMilisenda, Jose C.
dc.contributor.authorMunoz-Farjas, Elena
dc.contributor.authorPascual-Goni, Elba
dc.contributor.authorPerez-Larraya, Jaime Gallego
dc.contributor.authorSaiz, Albert
dc.contributor.authorDalmau, Josep
dc.contributor.authorBlanco, Yolanda
dc.contributor.authorGraus, Francesc
dc.contributor.authorMartinez-Hernandez, Eugenia
dc.date.accessioned2025-01-20T17:22:40Z
dc.date.available2025-01-20T17:22:40Z
dc.date.issued2023
dc.description.abstractBackground Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival.Methods This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain. Patients with pre-existing paraneoplastic syndromes or evidence of alternative causes for their neurological symptoms were excluded. We reviewed the clinical information, classified their clinical features, and determined the presence of neural antibodies. Neurological status was assessed by the treating physician one month after adverse event onset (as improvement vs no improvement) and at the last evaluation (complete recovery or modified Rankin Scale score decrease of at least 2 points, indicating good outcome, vs all other modified Rankin Scale scores, indicating poor outcome); if the participant had died, the date and cause of death were recorded. We used Fisher's exact tests and Mann-Whitney U tests to analyse clinical features, and multivariable logistic regression to analyse prognostic factors.Findings From Jan 1, 2018, until Feb 1, 2023, 83 patients with suspected neurological immune-related adverse events after use of immune checkpoint inhibitors were identified, of whom 64 patients were included. These patients had a median age of 67 years (IQR 59-74); 42 (66%) were male and 22 (34%) were female. The predominant tumours were lung cancer (30 [47%] patients), melanoma (13 [21%] patients), and renal cell carcinoma (seven [11%] patients). Neural antibodies were detected in 14 (22%) patients; 52 (81%) patients had CNS involvement and 12 (19%) had peripheral nervous system involvement. Encephalopathy occurred in 45 (70%) patients, 12 (27%) of whom had antibodies or well defined syndromes consistent with definite paraneoplastic or autoimmune encephalitis, 24 (53%) of whom had encephalitis without antibodies or clinical features characteristic of a defined syndrome, and nine (20%) of whom had encephalopathy without antibodies or inflammatory changes in CSF or brain MRI. Nine (14%) of 64 patients had combined myasthenia and myositis, five of them with myocarditis. Even though 58 (91%) of 64 patients received steroids and 31 (48%) of 64 received additional therapies, 18 (28%) did not improve during the first month after adverse event onset, and 11 of these 18 people died. At the last follow-up for the 53 remaining patients (median 6 months, IQR 3-13), 20 (38%) had a poor outcome (16 deaths, one related to a neurological immune-related adverse event). Mortality risk was increased in patients with lung cancer (vs those with other cancers: HR 2 center dot 5, 95% CI 1 center dot 1-6 center dot 0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5 center dot 0, 1 center dot 4-17 center dot 8 and HR 6 center dot 6, 1 center dot 4-31 center dot 0, respectively).Interpretation Most neurological immune-related adverse events involved the CNS and were antibody negative. The presence of myocarditis, myasthenia, and myositis, of encephalopathy without inflammatory changes, or of lung cancer were independent predictors of death.
dc.description.abstractMost deaths occurred during the first month of symptom onset. If our findings are replicated in additional cohorts, they could confirm that these patients need early and intensive treatment.
dc.fuente.origenWOS
dc.identifier.doi10.1016/S1474-4422(23)00335-6
dc.identifier.eissn1474-4465
dc.identifier.issn1474-4422
dc.identifier.urihttps://doi.org/10.1016/S1474-4422(23)00335-6
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/91488
dc.identifier.wosidWOS:001114539400001
dc.issue.numero12
dc.language.isoen
dc.pagina.final1159
dc.pagina.inicio1150
dc.revistaLancet neurology
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNeurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study
dc.typeartículo
dc.volumen22
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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