Abstract
Background
Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase of ICI oncological indications, their incidence is growing. Their recognition and management remain nevertheless challenging.
Methods
A national, web-based database was built to collect cases of neurological symptoms in patients receiving ICI and not attributable to other causes after an adequate workup.
Results
We identified 27 patients who developed nirAEs (20 males, median age 69 years). Patients received anti-PD1/PDL1 (78%), anti-CTLA4 (4%), or both (19%). Most common cancers were melanoma (30%) and non-small cell lung cancer (26%). Peripheral nervous system was mostly affected (78%). Median time to onset was 43.5 days and was shorter for peripheral versus central nervous system toxicities (36 versus 144.5 days, p = 0.045). Common manifestations were myositis (33%), inflammatory polyradiculoneuropathies (33%), and myasthenia gravis (19%), alone or in combination, but the spectrum of diagnoses was broad. Most patients received first-line glucocorticoids (85%) or IVIg (15%). Seven patients (26%) needed second-line treatments. At last follow-up, four (15%) patients were deceased (encephalitis, 1; myositis/myasthenia with concomitant myocarditis, 2; acute polyradiculoneuropathy, 1), while seven (26%) had a complete remission, eight (30%) partial improvement, and six (22%) stable/progressing symptoms. ICI treatment was discontinued in most patients (78%).
Conclusions
Neurological irAEs are rare but potentially fatal. They primarily affect neuromuscular structures but encompass a broad range of presentations. A prompt recognition is mandatory to timely withheld immunotherapy and administrate glucocorticoids. In corticoresistant or severely affected patients, second-line treatments with IVIg or plasmapheresis may result in additional benefit.
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Further anonymized clinical will be made available from the authors upon reasonable request.
Code availability
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Al.P., L.D., and E.M. designed and conceptualized the study; Al.P. and L.D. analyzed the data and drafted the manuscript for intellectual content; P.B., M.G., E.A., E.R., R.R., F.B., V.V., E.G., A.V., M.V., M.Z., V.P., B.G., C.C., and M.DV. had major role in the acquisition of data, interpreted the data, and revised the manuscript for intellectual content; An.P. interpreted the radiologic analyses and revised the manuscript for intellectual content.
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Diamanti, L., Picca, A., Bini, P. et al. Characterization and management of neurological adverse events during immune-checkpoint inhibitors treatment: an Italian multicentric experience. Neurol Sci 43, 2031–2041 (2022). https://doi.org/10.1007/s10072-021-05561-z
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DOI: https://doi.org/10.1007/s10072-021-05561-z