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.

Peripheral nervous system adverse events associated with immune checkpoint inhibitors / Rossi S.; Gelsomino F.; Rinaldi R.; Muccioli L.; Comito F.; Di Federico A.; De Giglio A.; Lamberti G.; Andrini E.; Mollica V.; D'Angelo R.; Baccari F.; Zenesini C.; Madia P.; Raschi E.; Cortelli P.; Ardizzoni A.; Guarino M.. - In: JOURNAL OF NEUROLOGY. - ISSN 0340-5354. - STAMPA. - 270:6(2023), pp. 2975-2986. [10.1007/s00415-023-11625-1]

Peripheral nervous system adverse events associated with immune checkpoint inhibitors

Rossi S.;Gelsomino F.;Muccioli L.;Comito F.;Di Federico A.;De Giglio A.;Lamberti G.;Andrini E.;Mollica V.;Zenesini C.;Madia P.;Raschi E.;Cortelli P.;Ardizzoni A.;
2023

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.
2023
Peripheral nervous system adverse events associated with immune checkpoint inhibitors / Rossi S.; Gelsomino F.; Rinaldi R.; Muccioli L.; Comito F.; Di Federico A.; De Giglio A.; Lamberti G.; Andrini E.; Mollica V.; D'Angelo R.; Baccari F.; Zenesini C.; Madia P.; Raschi E.; Cortelli P.; Ardizzoni A.; Guarino M.. - In: JOURNAL OF NEUROLOGY. - ISSN 0340-5354. - STAMPA. - 270:6(2023), pp. 2975-2986. [10.1007/s00415-023-11625-1]
Rossi S.; Gelsomino F.; Rinaldi R.; Muccioli L.; Comito F.; Di Federico A.; De Giglio A.; Lamberti G.; Andrini E.; Mollica V.; D'Angelo R.; Baccari F.; Zenesini C.; Madia P.; Raschi E.; Cortelli P.; Ardizzoni A.; Guarino M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/955584
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