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Current Cancer Therapy Reviews

Author(s): Felipe Fanine de Souza*, Julia Petry Trevisani, Letícia Caroline Breis, Luís Gustavo Marcelino Sizenando, Marco Antônio Machado Schlindwein, Paola Herreira Silva, Gustavo da Cunha Ribas and Marcus Vinicius Magno Gonçalves

DOI: 10.2174/1573394717666211108100559

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Central Nervous System Disorders Associated to Immune Checkpoint Inhibitors

Page: [87 - 94] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

New therapies and alternatives for the containment of tumor progression are being proposed for the treatment of cancer. In this context, monoclonal therapies using Immune Checkpoint Inhibitors (ICI) come as a therapeutic proposal. They are responsible for immunological control by blocking PD-1, PD-L1 and CTLA-4 molecules. However, among the effects caused by therapy, the use of medications is associated with neurological diseases reported as an adverse effect, affecting the Central Nervous System (CNS) and causing a wide range of symptoms. In this regard, the present bibliographic review presents the main CNS disorders associated with this therapy, in addition to the incidence, symptoms and treatment of these diseases.

Keywords: Immune checkpoints inhibitors, encephalitis, paraneoplastic syndromes, immunomodulators, neurological diseases, monoclonal antibodies.

[1]
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12(4): 252-64.
[http://dx.doi.org/10.1038/nrc3239] [PMID: 22437870]
[2]
El Osta B, Hu F, Sadek R, Chintalapally R, Tang SC. Not all immune-checkpoint inhibitors are created equal: Meta-analysis and systematic review of immune-related adverse events in cancer trials. Crit Rev Oncol Hematol 2017; 119: 1-12.
[http://dx.doi.org/10.1016/j.critrevonc.2017.09.002] [PMID: 29065979]
[3]
Shimozaki K, Sukawa Y, Beppu N, et al. Multiple immune-related adverse events and anti-tumor efficacy: Real-world data on various solid tumors. Cancer Manag Res 2020; 12: 4585-93.
[http://dx.doi.org/10.2147/CMAR.S247554] [PMID: 32606951]
[4]
Man J, Ritchie G, Links M, Lord S, Lee CK. Treatment-related toxicities of immune checkpoint inhibitors in advanced cancers: A meta-analysis. Asia Pac J Clin Oncol 2018; 14(3): 141-52.
[http://dx.doi.org/10.1111/ajco.12838] [PMID: 29349927]
[5]
Abdelhafeez AAM, Shohdy KS, Ibrahim W. Safety of combination immune checkpoint inhibitors compared to monotherapy; a systematic review and meta-analysis. Cancer Invest 2020; 38(3): 150-7.
[http://dx.doi.org/10.1080/07357907.2020.1714053] [PMID: 31977260]
[6]
Velasco R, Villagrán M, Jové M, et al. Encephalitis induced by immune checkpoint inhibitors: a systematic review. JAMA Neurol 2021; 78(7): 864-73.
[http://dx.doi.org/10.1001/jamaneurol.2021.0249] [PMID: 33720308]
[7]
Cuzzubbo S, Javeri F, Tissier M, et al. Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature. Eur J Cancer 2017; 73: 1-8.
[http://dx.doi.org/10.1016/j.ejca.2016.12.001] [PMID: 28064139]
[8]
Mancone S, Lycan T, Ahmed T, et al. Severe neurologic complications of immune checkpoint inhibitors: a single-center review. J Neurol 2018; 265(7): 1636-42.
[http://dx.doi.org/10.1007/s00415-018-8890-z] [PMID: 29761297]
[9]
Sato K, Mano T, Iwata A, Toda T. Neurological and related adverse events in immune checkpoint inhibitors: a pharmacovigilance study from the Japanese Adverse Drug Event Report database. J Neurooncol 2019; 145(1): 1-9.
[http://dx.doi.org/10.1007/s11060-019-03273-1] [PMID: 31452071]
[10]
Wang DY, Salem J-E, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol 2018; 4(12): 1721-8.
[http://dx.doi.org/10.1001/jamaoncol.2018.3923] [PMID: 30242316]
[11]
Larkin J, Chmielowski B, Lao CD, et al. Neurologic serious adverse events associated with nivolumab plus ipilimumab or nivolumab alone in advanced melanoma, including a case series of encephalitis. Oncologist 2017; 22(6): 709-18.
[http://dx.doi.org/10.1634/theoncologist.2016-0487] [PMID: 28495807]
[12]
Perrinjaquet C, Desbaillets N, Hottinger AF. Neurotoxicity associated with cancer immunotherapy: immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy. Curr Opin Neurol 2019; 32(3): 500-10.
[http://dx.doi.org/10.1097/WCO.0000000000000686] [PMID: 30893101]
[13]
Dalakas MC. Neurological complications of immune checkpoint inhibitors: what happens when you ‘take the brakes off’ the immune system. Ther Adv Neurol Disord 2018.
[http://dx.doi.org/10.1177/1756286418799864]
[14]
Salam S, Lavin T, Turan A. Limbic encephalitis following immunotherapy against metastatic malignant melanoma. BMJ Case Rep 2016; 2016: bcr2016215012.
[http://dx.doi.org/10.1136/bcr-2016-215012] [PMID: 27009198]
[15]
Vogrig A, Fouret M, Joubert B, Picard G, Rogemond V, Pinto AL. Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors. Neurol Neuroimmunol NeuroInflammation 2019.
[http://dx.doi.org/10.1212/NXI.0000000000000604]
[16]
Galmiche S, Lheure C, Kramkimel N, et al. Encephalitis induced by immune checkpoint inhibitors in metastatic melanoma: a monocentric retrospective study. J Eur Acad Dermatol Venereol 2019; 33(12): e440-3.
[http://dx.doi.org/10.1111/jdv.15756] [PMID: 31219194]
[17]
Santomasso BD. Anticancer drugs and the nervous system continuum. Minneap Minn 2020.
[18]
Astaras C, de Micheli R, Moura B, Hundsberger T, Hottinger AF. Neurologicaladverse events associated with immune checkpoint inhibitors: diagnosis and management. Curr Neurol Neurosci Rep 2018; 18(1): 3.
[http://dx.doi.org/10.1007/s11910-018-0810-1] [PMID: 29392441]
[19]
Hottinger AF. Neurologic complications of immune checkpoint inhibitors. Curr Opin Neurol 2016; 29(6): 806-12.
[http://dx.doi.org/10.1097/WCO.0000000000000391] [PMID: 27653290]
[20]
Vogrig A, Muñiz-Castrillo S, Joubert B, et al. Central nervous system complications associated with immune checkpoint inhibitors. J Neurol Neurosurg Psychiatry 2020; 91(7): 772-8.
[http://dx.doi.org/10.1136/jnnp-2020-323055] [PMID: 32312871]
[21]
Zurko J, Mehta A. Association of immune-mediated cerebellitis with immune checkpoint inhibitor therapy. Mayo Clin Proc Innov Qual Outcomes 2018; 2(1): 74-7.
[http://dx.doi.org/10.1016/j.mayocpiqo.2017.12.001] [PMID: 30225435]
[22]
Dubey D, David WS, Amato AA, et al. Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies. Neurology 2019; 93(11): e1093-103.
[http://dx.doi.org/10.1212/WNL.0000000000008091] [PMID: 31405908]
[23]
Reynolds KL, Guidon AC. Diagnosis and management of immune checkpoint inhibitor-associated neurologic toxicity: illustrative case and review of the literature. Oncologist 2019; 24(4): 435-43.
[http://dx.doi.org/10.1634/theoncologist.2018-0359] [PMID: 30482825]
[24]
Kim D. Posterior reversible encephalopathy syndrome induced by nivolumab immunotherapy for non-small-cell lung cancer. Clin Case Rep 2019; 7(5): 935-8.
[http://dx.doi.org/10.1002/ccr3.2122] [PMID: 31110718]
[25]
Dubey D, David WS, Reynolds KL, et al. Severe neurological toxicity of immune checkpoint inhibitors: growing spectrum. Ann Neurol 2020; 87(5): 659-69.
[http://dx.doi.org/10.1002/ana.25708] [PMID: 32086972]
[26]
Tchapyjnikov D, Borst AJ. Immune-related neurological symptoms in an adolescent patient receiving the checkpoint inhibitor nivolumab. J Immunother 2017; 40(7): 286-8.
[http://dx.doi.org/10.1097/CJI.0000000000000177] [PMID: 28604555]
[27]
Garcia CR, Jayswal R, Adams V, Anthony LB, Villano JL. Multiple sclerosis outcomes after cancer immunotherapy. Clin Transl Oncol 2019; 21(10): 1336-42.
[http://dx.doi.org/10.1007/s12094-019-02060-8] [PMID: 30788836]
[28]
Romeo MAL, Garassino MC, Moiola L, et al. Multiple sclerosis associated with pembrolizumab in a patient with non-small cell lung cancer. J Neurol 2019; 266(12): 3163-6.
[http://dx.doi.org/10.1007/s00415-019-09562-z] [PMID: 31586260]
[29]
Wilson MA, Guld K, Galetta S, et al. Acute visual loss after ipilimumab treatment for metastatic melanoma. J Immunother Cancer 2016; 4: 66.
[http://dx.doi.org/10.1186/s40425-016-0170-9] [PMID: 27777775]
[30]
Graus F, Dalmau J. Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat Rev Clin Oncol 2019; 16(9): 535-48.
[http://dx.doi.org/10.1038/s41571-019-0194-4] [PMID: 30867573]
[31]
Yshii LM, Gebauer CM, Pignolet B, et al. CTLA4 blockade elicits paraneoplastic neurological disease in a mouse model. Brain 2016; 139(11): 2923-34.
[http://dx.doi.org/10.1093/brain/aww225] [PMID: 27604307]
[32]
Gill A, Perez MA, Perrone CM, Bae CJ, Pruitt AA, Lancaster E. A case series of PD-1 inhibitor-associated paraneoplastic neurologic syndromes. J Neuroimmunol 2019; 334(April): 576980. [Internet].
[http://dx.doi.org/10.1016/j.jneuroim.2019.576980] [PMID: 31195181]
[33]
Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 2016; 17(7): 883-95.
[http://dx.doi.org/10.1016/S1470-2045(16)30098-5] [PMID: 27269741]
[34]
Williams TJ, Benavides DR, Patrice KA, et al. Association of autoimmune encephalitis with combined immune checkpoint inhibitor treatment for metastatic cancer. JAMA Neurol 2016; 73(8): 928-33.
[http://dx.doi.org/10.1001/jamaneurol.2016.1399] [PMID: 27271951]
[35]
Marini A, Bernardini A, Gigli GL, et al. Neurologic adverse events of immune checkpoint inhibitors: a systematic review. Neurology 2021; 96(16): 754-66.
[http://dx.doi.org/10.1212/WNL.0000000000011795] [PMID: 33653902]