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- Title
Peripheral nervous system adverse events associated with immune checkpoint inhibitors.
- Authors
Rossi, Simone; Gelsomino, Francesco; Rinaldi, Rita; Muccioli, Lorenzo; Comito, Francesca; Di Federico, Alessandro; De Giglio, Andrea; Lamberti, Giuseppe; Andrini, Elisa; Mollica, Veronica; D'Angelo, Roberto; Baccari, Flavia; Zenesini, Corrado; Madia, Pierandrea; Raschi, Emanuel; Cortelli, Pietro; Ardizzoni, Andrea; Guarino, Maria
- Abstract
Background: Immune checkpoint inhibitors (ICIs) represent an effective cancer immunotherapy yet are associated with immune-related adverse events (irAEs). The aim of this study was to characterize irAEs involving the peripheral nervous system (PNS-irAEs) in a real-world cohort of ICI-treated patients. Methods: Cancer patients treated with ICIs between January 2014 and March 2022 were included. Patients with PNS-irAEs were identified and divided into two groups: (1) cranial/peripheral neuropathies and (2) myasthenia gravis (MG) and/or myositis. Clinical characteristics and outcomes, measured with the modified Rankin Scale (mRS), were compared among the two groups. Results: Among 920 ICI-treated patients, 20 patients (2.17%) developed a PNS-irAEs. The median latency from ICI exposure was 8.8 weeks and the median time from onset to clinical nadir was 3.5 weeks. Eleven patients developed a neuropathy: polyneuropathy (n = 4), cranial neuropathy (n = 3), small-fiber neuropathy (n = 3), brachial plexopathy (n = 1). Nine patients presented MG and/or myositis: concomitant MG and myositis (n = 6), isolated myositis (n = 2), exacerbation of MG (n = 1). Immunosuppressive treatment and/or ICI withdrawal determined a significant clinical improvement, expressed by a mRS reduction, in the neuropathy group (p = 0.004), but not in the MG/myositis group (p = 0.11). Overall, death due to irAEs occurred in four patients (20%), all with MG/myositis. Compared to patients with neuropathies, those with MG/myositis had a shorter latency onset (p = 0.036), developed more frequently concomitant non-neurologic irAEs (p = 0.028) and showed a higher mortality rate (p = 0.026). Conclusions: In our large cohort of ICI-treated patients, 2.17% developed PNS-irAEs. Compared to ir-neuropathies, ir-MG/myositis tend to occur earlier from ICI exposure and present a worse response to treatment and a higher mortality.
- Subjects
PERIPHERAL nervous system; IMMUNE checkpoint inhibitors; BRACHIAL plexus neuropathies; MYASTHENIA gravis; DRUG side effects; IPILIMUMAB
- Publication
Journal of Neurology, 2023, Vol 270, Issue 6, p2975
- ISSN
0340-5354
- Publication type
Article
- DOI
10.1007/s00415-023-11625-1