Peripheral nervous system adverse events associated with immune checkpoint inhibitors.
Autoimmune neuropathies
ICI rechallenge
Myasthenia gravis
Myositis
Neuromuscular toxicities
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
04
01
2023
accepted:
09
02
2023
revised:
08
02
2023
medline:
18
5
2023
pubmed:
18
2
2023
entrez:
17
2
2023
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 36800019
doi: 10.1007/s00415-023-11625-1
pii: 10.1007/s00415-023-11625-1
pmc: PMC10188572
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2975-2986Informations de copyright
© 2023. The Author(s).
Références
Neurol Neuroimmunol Neuroinflamm. 2018 Dec 24;6(2):e535
pubmed: 30697585
Cancer Med. 2023 Feb;12(3):2281-2289
pubmed: 36128926
Ann Clin Transl Neurol. 2018 Sep 23;5(11):1421-1427
pubmed: 30480036
Eur J Cancer. 2017 Mar;73:1-8
pubmed: 28064139
Oncologist. 2021 Dec;26(12):1052-1061
pubmed: 34378270
Front Neurol. 2022 Apr 07;13:858628
pubmed: 35463153
Ann Oncol. 2017 Mar 1;28(3):673-675
pubmed: 27993808
Neurology. 2002 Jul 9;59(1):92-8
pubmed: 12105313
Front Neurol. 2022 Jul 19;13:936141
pubmed: 35928132
J Immunother Cancer. 2016 Jun 21;4:36
pubmed: 27330809
J Peripher Nerv Syst. 2019 Oct;24 Suppl 2:S74-S85
pubmed: 31393660
Nat Commun. 2020 Jul 30;11(1):3801
pubmed: 32732879
J Clin Med. 2022 Sep 23;11(19):
pubmed: 36233479
Clin Exp Immunol. 1990 Nov;82(2):284-8
pubmed: 2242609
Cancer Immunol Immunother. 2022 Apr;71(4):769-775
pubmed: 34515815
Neurology. 2021 Feb 9;96(6):e866-e875
pubmed: 33318162
J Peripher Nerv Syst. 2020 Jun;25(2):171-177
pubmed: 32166812
J Cancer Res Clin Oncol. 2022 Dec 10;:
pubmed: 36495331
Neurology. 2019 Sep 10;93(11):e1093-e1103
pubmed: 31405908
Clin Cancer Res. 2004 Nov 1;10(21):7270-5
pubmed: 15534101
Neurology. 2021 Apr 20;96(16):754-766
pubmed: 33653902
Cancers (Basel). 2019 Jan 24;11(2):
pubmed: 30682845
Ann Neurol. 2020 May;87(5):659-669
pubmed: 32086972
J Clin Oncol. 2021 Dec 20;39(36):4073-4126
pubmed: 34724392
Int J Mol Sci. 2020 Apr 26;21(9):
pubmed: 32357515
J Neurol. 2018 Jul;265(7):1636-1642
pubmed: 29761297
JAMA Oncol. 2018 Dec 1;4(12):1721-1728
pubmed: 30242316
JAMA Netw Open. 2022 Apr 1;5(4):e227722
pubmed: 35438755
N Engl J Med. 2018 Jan 11;378(2):158-168
pubmed: 29320654
Eur J Neurol. 2021 Nov;28(11):3556-3583
pubmed: 34327760
Stroke. 2009 Oct;40(10):3393-5
pubmed: 19679846
J Immunother Cancer. 2021 Jul;9(7):
pubmed: 34281989
Brain Commun. 2021 Oct 01;3(4):fcab220
pubmed: 34651126
J Clin Oncol. 2022 Oct 10;40(29):3439-3452
pubmed: 35658474
Semin Arthritis Rheum. 2014 Jun;43(6):792-6
pubmed: 24412588
Annu Rev Pathol. 2021 Jan 24;16:223-249
pubmed: 33197221
Arch Neurol. 2005 Mar;62(3):442-6
pubmed: 15767509
Neurol Sci. 2022 Apr;43(4):2339-2361
pubmed: 35175441
Arch Neurol. 2001 Jun;58(6):885-90
pubmed: 11405802
Neurology. 2017 Sep 12;89(11):1127-1134
pubmed: 28821685
Autoimmune Dis. 2011;2011:740583
pubmed: 21785709