Top

Open Access 03-09-2024 | Checkpoint Inhibitors | Review

Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients

Authors: Samuel Pichon, Pauline Aigrain, Charlotte Lacombe, Bruno Lemarchant, Emmanuel Ledoult, Vincent Koether, Amélie Leurs, Ghadi Zebian, David Launay, Benoit Gachet, Clémentine Levy

Published in: Journal of Neurology

Abstract

Objective

Describe the demographic data and clinical phenotype of cranial palsy induced by immune checkpoint inhibitors (CNP-ICI).

Methods

A systematic literature review of the literature was performed in Pubmed, Web of Science, and Embase, including 68 articles and 136 patients (PROSPERO no. CRD42024517262).

Results

Out of the 1205 articles screened, 68 articles were included after fulfilling the inclusion criteria, for a total of 136 patients. All articles were case reports and case series. In the cohort studied, 52% of patients were treated with anti PD-1/PDL-1 therapies, 14% with anti CTLA-4 therapies, and 34% with a combination of anti CTLA-4 and anti PD-1/PDL-1 therapies. The facial nerve was the most affected cranial nerve, involved in 38% of cases, followed by the optic nerve (35%), the cochleovestibular nerve (12%), and the abducens nerve (10%). The median time from the initial immune checkpoint inhibitor (ICI) injection to the onset CNP-ICI was 10 weeks (IQR 4–20). Magnetic resonance imaging demonstrated contrast enhancement or abnormal signal of the affected nerve in 43% of cases. Cerebrospinal fluid analysis indicated lymphocytic pleocytosis in 59% of cases. At the onset of immune-related adverse events, 89% of patients discontinued immunotherapy, and 92% received treatment for CNP-ICI. Treatment regimens included corticosteroids in 86% of cases, intravenous immunoglobulin in 21%, and plasma exchange in 5.1%. Among the whole population, 33% achieved recovery, 52% showed clinical improvement, 16% remained stable, and 3% experienced worsening of their condition. Rechallenge with immunotherapy was significantly associated with the emergence of new immune-related Adverse Events (irAEs).

Conclusion

ICI therapy may lead to cranial nerve involvement, particularly affecting the facial nerve, typically presenting around 10 weeks after treatment initiation. While corticosteroid therapy often resulted in patient improvement, rechallenging with ICIs were associated with new irAEs.

Available only for authorised users

Robert C (2020) A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun 11:3801. https://doi.org/10.1038/s41467-020-17670-yCrossRefPubMedPubMedCentral

Mamdani H, Matosevic S, Khalid AB et al (2022) Immunotherapy in lung cancer: current landscape and future directions. Front Immunol 13:823618CrossRefPubMedPubMedCentral

Hodi FS, Chiarion-Sileni V, Gonzalez R et al (2018) Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol 19:1480–1492. https://doi.org/10.1016/S1470-2045(18)30700-9CrossRefPubMed

Ribas A, Wolchok JD (2018) Cancer immunotherapy using checkpoint blockade. Science 359:1350–1355. https://doi.org/10.1126/science.aar4060CrossRefPubMedPubMedCentral

Michot JM, Bigenwald C, Champiat S et al (2016) Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 54:139–148. https://doi.org/10.1016/j.ejca.2015.11.016CrossRefPubMed

Gougis P, Jochum F, Abbar B et al (2024) Clinical spectrum and evolution of immune-checkpoint inhibitors toxicities over a decade—a worldwide perspective. eClinicalMedicine 70:102536. https://doi.org/10.1016/j.eclinm.2024.102536CrossRefPubMedPubMedCentral

Cuzzubbo S, Javeri F, Tissier M et al (2017) Neurological adverse events associated with immune checkpoint inhibitors: review of the literature. Eur J Cancer 73:1–8. https://doi.org/10.1016/j.ejca.2016.12.001CrossRefPubMed

Xu M, Nie Y, Yang Y et al (2019) Risk of neurological toxicities following the use of different immune checkpoint inhibitor regimens in solid tumors: a systematic review and meta-analysis. Neurologist 24:75–83. https://doi.org/10.1097/NRL.0000000000000230CrossRefPubMed

Vogrig A, Muñiz-Castrillo S, Joubert B et al (2021) Cranial nerve disorders associated with immune checkpoint inhibitors. Neurology. https://doi.org/10.1212/WNL.0000000000011340CrossRefPubMed

10.

Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. https://doi.org/10.1136/bmj.n71CrossRefPubMedPubMedCentral

11.

Murad MH, Sultan S, Haffar S, Bazerbachi F (2018) Methodological quality and synthesis of case series and case reports. BMJ Evid-Based Med 23:60–63. https://doi.org/10.1136/bmjebm-2017-110853CrossRefPubMedPubMedCentral

12.

Oguri T, Sasada S, Shimizu S et al (2021) A case of Guillain–Barré syndrome and Stevens-Johnson syndrome/toxic epidermal necrosis overlap after pembrolizumab treatment. J Investig Med High Impact Case Rep 9:232470962110374. https://doi.org/10.1177/23247096211037462CrossRef

13.

Xie K, Kong C, Mehta MC (2020) A case of melanoma-associated retinopathy, uveitis, and optic neuritis associated with pembrolizumab, managed with topical, intravitreal, and intravenous steroids. J Vitreoretin Dis 4:220–226. https://doi.org/10.1177/2474126419886154CrossRefPubMed

14.

Ogawa M, Tateishi Y, Suzuki H et al (2020) A case of non-small-cell lung cancer with acute optic neuritis observed after pembrolizumab treatment. Haigan 60:385–389. https://doi.org/10.2482/haigan.60.385CrossRef

15.

McNeill CJ, Fehmi J, Gladwin J, Price C (2019) A rare case of Miller Fisher variant of Guillain–Barré syndrome (GBS) induced by a checkpoint inhibitor. BMJ Case Rep 12:e229443. https://doi.org/10.1136/bcr-2019-229443CrossRefPubMedPubMedCentral

16.

Wilson MA, Guld K, Galetta S et al (2016) Acute visual loss after ipilimumab treatment for metastatic melanoma. J Immunother Cancer 4:66. https://doi.org/10.1186/s40425-016-0170-9CrossRefPubMedPubMedCentral

17.

Kichloo A, Albosta MS, Jamal SM et al (2020) Atezolizumab-induced Bell’s palsy in a patient with small cell lung cancer. J Investig Med High Impact Case Rep 8:232470962096501. https://doi.org/10.1177/2324709620965010CrossRef

18.

Liao B, Shroff S, Kamiya-Matsuoka C, Tummala S (2014) Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma. Neuro-Oncol 16:589–593. https://doi.org/10.1093/neuonc/nou001CrossRefPubMedPubMedCentral

19.

Zieman D, Frankel AE (2019) Autoimmune Bell’s palsy following immunotherapy for metastatic melanoma: a report of 2 cases. J Immunother 42:318–320. https://doi.org/10.1097/CJI.0000000000000291CrossRefPubMed

20.

Takemura K, Yamanaka T, Hayashida M et al (2023) Bell’s palsy during rechallenge of immune checkpoint inhibitor. IJU Case Rep 6:144–146. https://doi.org/10.1002/iju5.12572CrossRefPubMedPubMedCentral

21.

Numata S, Iwata Y, Okumura R et al (2018) Bilateral anterior uveitis and unilateral facial palsy due to ipilimumab for metastatic melanoma in an individual with human leukocyte antigen DR4: a case report. J Dermatol 45:113–114. https://doi.org/10.1111/1346-8138.13779CrossRefPubMed

22.

Altman AL, Golub JS, Pensak ML, Samy RN (2015) Bilateral facial palsy following ipilimumab infusion for melanoma. Otolaryngol Neck Surg 153:894–895. https://doi.org/10.1177/0194599815606701CrossRef

23.

Vicente-Pascual M, Molins-Rojas C, Rosas-Soto K et al (2021) Bilateral optic neuritis secondary to immune etiology by anti-PD-L1 antibody. J Neuroophthalmol 41:e177–e179. https://doi.org/10.1097/WNO.0000000000001029CrossRefPubMed

24.

Kartal Ö, Ataş E (2018) Bilateral optic neuritis secondary to nivolumab therapy: a case report. Medicina (Mex) 54:82. https://doi.org/10.3390/medicina54050082CrossRef

25.

Willegers T, Janssen JBE, Boers-Sonderen MJ, Bekkers S (2020) Bilateral vocal cord paralysis due to an immune-related adverse event of nivolumab: a case report. J Immunother 43:93–94. https://doi.org/10.1097/CJI.0000000000000310CrossRefPubMed

26.

Hou Y, Su Q, Tang S, Li H (2022) Camrelizumab-induced isolate abducens neuritis: a rare ophthalmic immune-related adverse events. Brain Sci 12:1242. https://doi.org/10.3390/brainsci12091242CrossRefPubMedPubMedCentral

27.

Wang Q, Yan X, Li J (2022) Camrelizumab-induced isolated abducens nerve palsy. Adv Drug React J. https://doi.org/10.3760/cma.j.cn114015-20220119-00049CrossRef

28.

Wako S, Ikeguchi R, Toda K et al (2023) Characteristic cerebrospinal fluid findings in immune checkpoint inhibitor-related peripheral neuropathy: a case report. J Neuroimmunol 374:578010. https://doi.org/10.1016/j.jneuroim.2022.578010CrossRefPubMed

29.

Diamanti L, Picca A, Bini P et al (2022) Characterization and management of neurological adverse events during immune-checkpoint inhibitors treatment: an Italian multicentric experience. Neurol Sci 43:2031–2041. https://doi.org/10.1007/s10072-021-05561-zCrossRefPubMed

30.

Patel AS, Snook RJ, Sehdev A (2019) Chronic inflammatory demyelinating polyradiculoneuropathy secondary to immune checkpoint inhibitors in melanoma patients. Discov Med 28:107–111PubMed

31.

Lemasson J, Cuzzubbo S, Doucet L et al (2019) Cochleovestibular toxicity induced by immune checkpoint inhibition: a case series. Eur J Cancer 117:116–118. https://doi.org/10.1016/j.ejca.2019.05.022CrossRefPubMed

32.

Diamantopoulos PT, Tsatsou K, Benopoulou O et al (2020) Concomitant development of neurologic and cardiac immune-related adverse effects in patients treated with immune checkpoint inhibitors for melanoma. Melanoma Res 30:484–491. https://doi.org/10.1097/CMR.0000000000000681CrossRefPubMed

33.

Bolz S, Ramakrishnan T, Fleischer M et al (2021) Detect it so you can treat it: A case series and proposed checklist to detect neurotoxicity in checkpoint therapy. eNeurologicalSci 22:100324. https://doi.org/10.1016/j.ensci.2021.100324CrossRefPubMedPubMedCentral

34.

Zecchini JM, Kim S, Yum K, Friedlander P (2018) Development of Bell’s palsy after treatment with ipilimumab and nivolumab for metastatic melanoma: a case report. J Immunother 41:39–41. https://doi.org/10.1097/CJI.0000000000000184CrossRefPubMed

35.

Nowosielski M, Di Pauli F, Iglseder S et al (2020) Encephalomyeloneuritis and arthritis after treatment with immune checkpoint inhibitors. Neurol Neuroimmunol Neuroinflamm 7:e773. https://doi.org/10.1212/NXI.0000000000000773CrossRefPubMedPubMedCentral

36.

Yost MD, Chou CZ, Botha H et al (2017) Facial diplegia after pembrolizumab treatment. Muscle Nerve. https://doi.org/10.1002/mus.25663CrossRefPubMed

37.

Yuen C, Reid P, Zhang Z et al (2019) Facial palsy induced by checkpoint blockade: a single center retrospective study. J Immunother 42:94–96. https://doi.org/10.1097/CJI.0000000000000254CrossRefPubMed

38.

Green KE, Levine AM, Ward JH, Kaufman DI (2019) GQ1b-seronegative miller fisher syndrome associated with pembrolizumab. J Neuroophthalmol 39:394–396. https://doi.org/10.1097/WNO.0000000000000755CrossRefPubMed

39.

Ong S, Chapman J, Young G, Mansy T (2018) Guillain–Barré-like syndrome during pembrolizumab treatment. Muscle Nerve. https://doi.org/10.1002/mus.26101CrossRefPubMed

40.

Francis JH, Jaben K, Santomasso BD et al (2020) Immune checkpoint inhibitor-associated optic neuritis. Ophthalmology 127:1585–1589. https://doi.org/10.1016/j.ophtha.2020.05.003CrossRefPubMed

41.

Beninato T, Fucà G, Di Guardo L et al (2021) Immune-related Bell’s palsy in melanoma patients treated with immune checkpoint inhibitors. Melanoma Res 31:178–180. https://doi.org/10.1097/CMR.0000000000000715CrossRefPubMed

42.

Yeh OL, Francis CE (2015) Ipilimumab-associated bilateral optic neuropathy. J Neuroophthalmol 35:144–147. https://doi.org/10.1097/WNO.0000000000000217CrossRefPubMed

43.

Jaben KA, Francis JH, Shoushtari AN, Abramson DH (2020) Isolated abducens nerve palsy following pembrolizumab. Neuro-Ophthalmol 44:182–185. https://doi.org/10.1080/01658107.2019.1566385CrossRef

44.

Makri OE, Dimitrakopoulos F-I, Tsapardoni F et al (2022) Isolated optic neuritis after pembrolizumab administration for non-small-cell lung carcinoma. Int J Neurosci 132:643–648. https://doi.org/10.1080/00207454.2020.1831489CrossRefPubMed

45.

Manousakis G, Koch J, Sommerville RB et al (2013) Multifocal radiculoneuropathy during ipilimumab treatment of melanoma. Muscle Nerve 48:440–444. https://doi.org/10.1002/mus.23830CrossRefPubMed

46.

Siegel CH, Finn RS, Ho MG (2018) Multiple cranial neuropathies from nivolumab in a patient with metastatic hepatocellular carcinoma. Mayo Clin Proc 93:540–541. https://doi.org/10.1016/j.mayocp.2018.01.001CrossRefPubMed

47.

Nishimura T, Sakatani T, Takeshima H et al (2022) Multiple cranial neuropathies similar to orbital apex syndrome associated with pembrolizumab: a case report. Case Rep Oncol 15:868–873. https://doi.org/10.1159/000526901CrossRefPubMedPubMedCentral

48.

Sun MM, Seleme N, Chen JJ et al (2021) Neuro-ophthalmic complications in patients treated with CTLA-4 and PD-1/PD-L1 checkpoint blockade. J Neuroophthalmol 41:519–530. https://doi.org/10.1097/WNO.0000000000001148CrossRefPubMed

49.

Kao JC, Liao B, Markovic SN et al (2017) Neurological complications associated with anti-programmed death 1 (PD-1) antibodies. JAMA Neurol 74:1216. https://doi.org/10.1001/jamaneurol.2017.1912CrossRefPubMedPubMedCentral

50.

Plaçais L, Michot J-M, Champiat S et al (2021) Neurological complications induced by immune checkpoint inhibitors: a comprehensive descriptive case-series unravelling high risk of long-term sequelae. Brain Commun 3:fcab220. https://doi.org/10.1093/braincomms/fcab220CrossRefPubMedPubMedCentral

51.

Farina A, Birzu C, Elsensohn M-H et al (2023) Neurological outcomes in immune checkpoint inhibitor-related neurotoxicity. Brain Commun 5:fcad169. https://doi.org/10.1093/braincomms/fcad169CrossRefPubMedPubMedCentral

52.

Zimmer L, Goldinger SM, Hofmann L et al (2016) Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer 60:210–225. https://doi.org/10.1016/j.ejca.2016.02.024CrossRefPubMed

53.

Dinoto A, McKeon A, Vattemi G et al (2022) Neuronal intermediate filament paraneoplastic autoimmunity complicating avelumab therapy of Merkel cell carcinoma. J Neuroimmunol 368:577882. https://doi.org/10.1016/j.jneuroim.2022.577882CrossRefPubMedPubMedCentral

54.

Cordes LM, Davarpanah NN, Reoma LB et al (2020) Neurotoxicities associated with checkpoint inhibitors: two case reports and a review of the literature. Clin Case Rep 8:24–32. https://doi.org/10.1002/ccr3.2534CrossRefPubMed

55.

Duong SL, Barbiero FJ, Nowak RJ, Baehring JM (2021) Neurotoxicities associated with immune checkpoint inhibitor therapy. J Neurooncol 152:265–277. https://doi.org/10.1007/s11060-021-03695-wCrossRefPubMed

56.

Nukui T, Nakayama Y, Yamamoto M et al (2018) Nivolumab-induced acute demyelinating polyradiculoneuropathy mimicking Guillain–Barré syndrome. J Neurol Sci 390:115–116. https://doi.org/10.1016/j.jns.2018.04.028CrossRefPubMed

57.

Noble CW, Gangaputra SS, Thompson IA et al (2020) Ocular adverse events following use of immune checkpoint inhibitors for metastatic malignancies. Ocul Immunol Inflamm 28:854–859. https://doi.org/10.1080/09273948.2019.1583347CrossRefPubMed

58.

Parikh RA, Chaon BC, Berkenstock MK (2021) Ocular complications of checkpoint inhibitors and immunotherapeutic agents: a case series. Ocul Immunol Inflamm 29:1585–1590. https://doi.org/10.1080/09273948.2020.1766082CrossRefPubMed

59.

Kim JM, Materin MA, Sznol M et al (2019) Ophthalmic immune-related adverse events of immunotherapy: a single-site case series. Ophthalmology 126:1058–1062. https://doi.org/10.1016/j.ophtha.2019.01.031CrossRefPubMed

60.

Mori S, Kurimoto T, Ueda K et al (2018) Optic neuritis possibly induced by anti-PD-L1 antibody treatment in a patient with non-small cell lung carcinoma. Case Rep Ophthalmol 9:348–356. https://doi.org/10.1159/000491075CrossRefPubMedPubMedCentral

61.

SengulSamanci N, Ozan T, Çelik E, Demirelli FH (2020) Optic neuritis related to atezolizumab treatment in a patient with metastatic non–small-cell lung cancer. JCO Oncol Pract 16:96–98. https://doi.org/10.1200/JOP.19.00438CrossRef

62.

Mirabile A, Brioschi E, Ducceschi M et al (2019) PD-1 inhibitors-related neurological toxicities in patients with non-small-cell lung cancer: a literature review. Cancers 11:296. https://doi.org/10.3390/cancers11030296CrossRefPubMedPubMedCentral

63.

De Maleissye M-F, Nicolas G, Saiag P (2016) Pembrolizumab-induced demyelinating polyradiculoneuropathy. N Engl J Med 375:296–297. https://doi.org/10.1056/NEJMc1515584CrossRefPubMed

64.

Bruno F, Palmiero RA, Ferrero B et al (2021) Pembrolizumab-induced isolated cranial neuropathy: a rare case report and review of literature. Front Neurol 12:669493. https://doi.org/10.3389/fneur.2021.669493CrossRefPubMedPubMedCentral

65.

Daetwyler E, Zippelius A, Meyer P, Läubli H (2023) Pembrolizumab-induced optic neuropathy—a case report. Front Immunol 14:1171981. https://doi.org/10.3389/fimmu.2023.1171981CrossRefPubMedPubMedCentral

66.

Rossi S, Gelsomino F, Rinaldi R et al (2023) Peripheral nervous system adverse events associated with immune checkpoint inhibitors. J Neurol 270:2975–2986. https://doi.org/10.1007/s00415-023-11625-1CrossRefPubMedPubMedCentral

67.

Ahluwalia A, Kohli AA (2021) Photopsias in the setting of nivolumab therapy. J Neuroophthalmol 41:e25–e26. https://doi.org/10.1097/WNO.0000000000000909CrossRefPubMed

68.

Kawakado K, Tamura T, Nakanishi M et al (2021) Retrobulbar optic neuritis induced by pembrolizumab in a patient with lung adenocarcinoma. Intern Med 60:3941–3945. https://doi.org/10.2169/internalmedicine.7425-21CrossRefPubMedPubMedCentral

69.

Boisseau W, Touat M, Berzero G et al (2017) Safety of treatment with nivolumab after ipilimumab-related meningoradiculitis and bilateral optic neuropathy. Eur J Cancer 83:28–31. https://doi.org/10.1016/j.ejca.2017.05.036CrossRefPubMed

70.

Wilson R, Menassa DA, Davies AJ et al (2018) Seronegative antibody-mediated neurology after immune checkpoint inhibitors. Ann Clin Transl Neurol 5:640–645. https://doi.org/10.1002/acn3.547CrossRefPubMedPubMedCentral

71.

Kambayashi Y, Fujimura T, Kuroda H et al (2020) Severe demyelinating neuropathy in an advanced melanoma patient treated with nivolumab plus ipilimumab combined therapy. Case Rep Oncol 13:474–477. https://doi.org/10.1159/000506976CrossRefPubMedPubMedCentral

72.

Bompaire F, Mateus C, Taillia H et al (2012) Severe meningo-radiculo-nevritis associated with ipilimumab. Invest New Drugs 30:2407–2410. https://doi.org/10.1007/s10637-011-9787-1CrossRefPubMed

73.

Mancone S, Lycan T, Ahmed T et al (2018) Severe neurologic complications of immune checkpoint inhibitors: a single-center review. J Neurol 265:1636–1642. https://doi.org/10.1007/s00415-018-8890-zCrossRefPubMed

74.

Dubey D, David WS, Reynolds KL et al (2020) Severe neurological toxicity of immune checkpoint inhibitors: growing spectrum. Ann Neurol 87:659–669. https://doi.org/10.1002/ana.25708CrossRefPubMed

75.

Ruff MW, Mauermann ML (2018) The mayo clinic experience with the neurological complications of the CTLA-4 inhibitor ipilimumab. Neurologist 23:98–99. https://doi.org/10.1097/NRL.0000000000000176CrossRefPubMed

76.

Missori P, Ambrosone A, Cristofani L et al (2022) Third cranial nerve palsy after monoclonal antibody therapy for lung cancer: a case report. Case Rep Ophthalmol 13:282–285. https://doi.org/10.1159/000524114CrossRefPubMedPubMedCentral

77.

Dubey D, David WS, Amato AA et al (2019) Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies. Neurology. https://doi.org/10.1212/WNL.0000000000008091CrossRefPubMed

78.

Aya F, Ruiz-Esquide V, Viladot M et al (2017) Vasculitic neuropathy induced by pembrolizumab. Ann Oncol 28:433–434. https://doi.org/10.1093/annonc/mdw613CrossRefPubMed

79.

Gaudin RA, Jowett N, Banks CA et al (2016) Bilateral facial paralysis: a 13-year experience. Plast Reconstr Surg 138:879–887. https://doi.org/10.1097/PRS.0000000000002599CrossRefPubMed

80.

Yanagihara N, Mori H, Kozawa T et al (1984) Bell’s palsy: nonrecurrent v recurrent and unilateral v bilateral. Arch Otolaryngol Head Neck Surg 110:374–377. https://doi.org/10.1001/archotol.1984.00800320028006CrossRef

81.

Allenbach Y, Anquetil C, Manouchehri A et al (2020) Immune checkpoint inhibitor-induced myositis, the earliest and most lethal complication among rheumatic and musculoskeletal toxicities. Autoimmun Rev 19:102586. https://doi.org/10.1016/j.autrev.2020.102586CrossRefPubMed

82.

Touat M, Maisonobe T, Knauss S et al (2018) Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer. Neurology. https://doi.org/10.1212/WNL.0000000000006124CrossRefPubMedPubMedCentral

83.

Salem J-E, Bretagne M, Abbar B et al (2023) Abatacept/ruxolitinib and screening for concomitant respiratory muscle failure to mitigate fatality of immune-checkpoint inhibitor myocarditis. Cancer Discov 13:1100–1115. https://doi.org/10.1158/2159-8290.CD-22-1180CrossRefPubMed

84.

Lehmann LH, Heckmann MB, Bailly G et al (2023) Cardiomuscular biomarkers in the diagnosis and prognostication of immune checkpoint inhibitor myocarditis. Circulation 148:473–486. https://doi.org/10.1161/CIRCULATIONAHA.123.062405CrossRefPubMedPubMedCentral

85.

Clarke JL, Perez HR, Jacks LM et al (2010) Leptomeningeal metastases in the MRI era. Neurology 74:1449–1454. https://doi.org/10.1212/WNL.0b013e3181dc1a69CrossRefPubMedPubMedCentral

86.

Pavlidis N (2004) The diagnostic and therapeutic management of leptomeningeal carcinomatosis. Ann Oncol 15:iv285–iv291. https://doi.org/10.1093/annonc/mdh941CrossRefPubMed

87.

Giles AJ, Hutchinson M-KND, Sonnemann HM et al (2018) Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J Immunother Cancer 6:51. https://doi.org/10.1186/s40425-018-0371-5CrossRefPubMedPubMedCentral

88.

Maeda N, Maruhashi T, Sugiura D et al (2019) Glucocorticoids potentiate the inhibitory capacity of programmed cell death 1 by up-regulating its expression on T cells. J Biol Chem 294:19896–19906. https://doi.org/10.1074/jbc.RA119.010379CrossRefPubMedPubMedCentral

89.

Haanen JBAG, Carbonnel F, Robert C et al (2017) Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:iv119–iv142. https://doi.org/10.1093/annonc/mdx225CrossRefPubMed

90.

Schneider BJ, Naidoo J, Santomasso BD et al (2021) Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: asco guideline update. J Clin Oncol 39:4073–4126. https://doi.org/10.1200/JCO.21.01440CrossRefPubMed

91.

Tomsitz D, Ruf T, Zierold S et al (2023) Steroid-refractory immune-related adverse events induced by checkpoint inhibitors. Cancers 15:2538. https://doi.org/10.3390/cancers15092538CrossRefPubMedPubMedCentral

92.

Janssen JBE, Leow TYS, Herbschleb KH et al (2021) Immune checkpoint inhibitor–related guillain-barré syndrome: a case series and review of the literature. J Immunother 44:276–282. https://doi.org/10.1097/CJI.0000000000000364CrossRefPubMed

93.

Katsumoto TR, Wilson KL, Giri VK et al (2022) Plasma exchange for severe immune-related adverse events from checkpoint inhibitors: an early window of opportunity? Immunother Adv 2:ltac012. https://doi.org/10.1093/immadv/ltac012CrossRefPubMedPubMedCentral

94.

Zhao Q, Zhang J, Xu L et al (2021) Safety and efficacy of the rechallenge of immune checkpoint inhibitors after immune-related adverse events in patients with cancer: a systemic review and meta-analysis. Front Immunol 12:730320. https://doi.org/10.3389/fimmu.2021.730320CrossRefPubMedPubMedCentral

95.

Dolladille C, Ederhy S, Sassier M et al (2020) Immune checkpoint inhibitor rechallenge after immune-related adverse events in patients with cancer. JAMA Oncol 6:865. https://doi.org/10.1001/jamaoncol.2020.0726CrossRefPubMed

96.

Owen CN, Bai X, Quah T et al (2021) Delayed immune-related adverse events with anti-PD-1-based immunotherapy in melanoma. Ann Oncol 32:917–925. https://doi.org/10.1016/j.annonc.2021.03.204CrossRefPubMed

97.

Couey MA, Bell RB, Patel AA et al (2019) Delayed immune-related events (DIRE) after discontinuation of immunotherapy: diagnostic hazard of autoimmunity at a distance. J Immunother Cancer 7:165. https://doi.org/10.1186/s40425-019-0645-6CrossRefPubMedPubMedCentral

98.

Wang DY, Salem J-E, Cohen JV et al (2018) Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol 4:1721. https://doi.org/10.1001/jamaoncol.2018.3923CrossRefPubMedPubMedCentral

99.

Fonseca E, Cabrera-Maqueda JM, Ruiz-García R et al (2023) Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study. Lancet Neurol 22:1150–1159. https://doi.org/10.1016/S1474-4422(23)00335-6CrossRefPubMed

100.

Dall’Olio FG, Rizzo A, Mollica V et al (2021) Immortal time bias in the association between toxicity and response for immune checkpoint inhibitors: a meta-analysis. Immunotherapy 13:257–270. https://doi.org/10.2217/imt-2020-0179CrossRefPubMed

101.

Kfoury M, Najean M, Lappara A et al (2022) Analysis of the association between prospectively collected immune-related adverse events and survival in patients with solid tumor treated with immune-checkpoint blockers, taking into account immortal-time bias. Cancer Treat Rev 110:102452. https://doi.org/10.1016/j.ctrv.2022.102452CrossRefPubMed

102.

Zhong L, Wu Q, Chen F et al (2021) Immune-related adverse events: promising predictors for efficacy of immune checkpoint inhibitors. Cancer Immunol Immunother 70:2559–2576. https://doi.org/10.1007/s00262-020-02803-5CrossRefPubMedPubMedCentral

103.

Maher VE, Fernandes LL, Weinstock C et al (2019) Analysis of the association between adverse events and outcome in patients receiving a programmed death protein 1 or programmed death ligand 1 antibody. J Clin Oncol 37:2730–2737. https://doi.org/10.1200/JCO.19.00318CrossRefPubMed

104.

Verheijden RJ, Van Eijs MJM, May AM et al (2023) Immunosuppression for immune-related adverse events during checkpoint inhibition: an intricate balance. NPJ Precis Oncol 7:41. https://doi.org/10.1038/s41698-023-00380-1CrossRefPubMedPubMedCentral

105.

Tokunaga A, Sugiyama D, Maeda Y et al (2019) Selective inhibition of low-affinity memory CD8+ T cells by corticosteroids. J Exp Med 216:2701–2713. https://doi.org/10.1084/jem.20190738CrossRefPubMedPubMedCentral

106.

Iorgulescu JB, Gokhale PC, Speranza MC et al (2021) Concurrent dexamethasone limits the clinical benefit of immune checkpoint blockade in glioblastoma. Clin Cancer Res 27:276–287. https://doi.org/10.1158/1078-0432.CCR-20-2291CrossRefPubMed

107.

Tarhini AA, Kang N, Lee SJ et al (2021) Immune adverse events (irAEs) with adjuvant ipilimumab in melanoma, use of immunosuppressants and association with outcome: ECOG-ACRIN E1609 study analysis. J Immunother Cancer 9:e002535. https://doi.org/10.1136/jitc-2021-002535CrossRefPubMedPubMedCentral

108.

Faje AT, Lawrence D, Flaherty K et al (2018) High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma. Cancer 124:3706–3714. https://doi.org/10.1002/cncr.31629CrossRefPubMed

109.

Simpson TR, Li F, Montalvo-Ortiz W et al (2013) Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma. J Exp Med 210:1695–1710. https://doi.org/10.1084/jem.20130579CrossRefPubMedPubMedCentral

110.

Nishimura H, Nose M, Hiai H et al (1999) Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11:141–151. https://doi.org/10.1016/S1074-7613(00)80089-8CrossRefPubMed

111.

Ramos-Casals M, Brahmer JR, Callahan MK et al (2020) Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primer 6:38. https://doi.org/10.1038/s41572-020-0160-6CrossRef

112.

Axelrod ML, Meijers WC, Screever EM et al (2022) T cells specific for α-myosin drive immunotherapy-related myocarditis. Nature 611:818–826. https://doi.org/10.1038/s41586-022-05432-3CrossRefPubMedPubMedCentral

113.

Fenioux C, Abbar B, Boussouar S et al (2024) Publisher correction: thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis. Nat Med 30:910–910. https://doi.org/10.1038/s41591-023-02771-0CrossRefPubMed

Title: Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients
Authors: Samuel Pichon
Pauline Aigrain
Charlotte Lacombe
Bruno Lemarchant
Emmanuel Ledoult
Vincent Koether
Amélie Leurs
Ghadi Zebian
David Launay
Benoit Gachet
Clémentine Levy
Publication date: 03-09-2024
Publisher: Springer Berlin Heidelberg
Keyword: Checkpoint Inhibitors
Published in: Journal of Neurology
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-024-12660-2

Advances in Alzheimer's

Alzheimer's Disease
Independent Medical Education

Alzheimer's research and care is changing rapidly. Keep up with the latest developments from key international conferences, together with expert insights on how to integrate these advances into practice.

This content is intended for healthcare professionals outside of the UK.

Supported by:

Lilly

Developed by: Springer Healthcare IME

Learn more

EASD 2024

Springer Medicine

Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients

Abstract

Objective

Methods

Results

Conclusion

Advances in Alzheimer's

EASD 2024

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Advances in Alzheimer's