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Characterization and management of neurological adverse events during immune-checkpoint inhibitors treatment: an Italian multicentric experience

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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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Availability of data and material

Further anonymized clinical will be made available from the authors upon reasonable request.

Code availability

Not applicable.

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Author notes

  1. L. Diamanti and A. Picca contributed equally to this work.

Authors and Affiliations

  1. “C. Mondino” National Neurological Institute, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy

    Luca Diamanti, Alberto Picca, Paola Bini, Matteo Gastaldi, Enrico Alfonsi, Anna Pichiecchio & Enrico Marchioni

  2. Neurology Unit, Ospedale San Giacomo, Novi Ligure, ASL Alessandria, Italy

    Eugenia Rota

  3. Castelfranco Veneto Hospital, Castelfranco Veneto, Italy

    Roberta Rudà

  4. University and City of Health and Science of Turin, Turin, Italy

    Francesco Bruno

  5. IRCCS Regina Elena National Cancer Institute, Rome, Italy

    Veronica Villani & Edvina Galiè

  6. Clinical Neurology Unit, Azienda Sanitaria Universitaria Friuli Centrale, Presidio Ospedaliero Santa Maria della Misericordia, Udine, Italy

    Alberto Vogrig & Mariarosaria Valente

  7. UOC Neurologia O.S.A. - Azienda Ospedale Università Di Padova, Padua, Italy

    Marco Zoccarato

  8. Department of Emergency, Neurology Unit, Santa Chiara Hospital, Trento, Italy

    Valentina Poretto & Bruno Giometto

  9. Medical Oncology, IRCCS National Cancer Institute, Milan, Italy

    Carolina Cimminiello & Michele Del Vecchio

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  1. Luca Diamanti
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Contributions

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.

Corresponding author

Correspondence to Alberto Picca.

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The retrospective study was approved by institutional ethic committee (No. 20190026431).

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Informed consent was waived for de-identified, retrospective data.

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The authors declare no competing interests.

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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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