Myasthenia gravis during treatment with anti-PD-1 - succesfull treatment using pirydostygminum – case report and literature review
DOI:
https://doi.org/10.12775/JEHS.2022.12.12.001Keywords
carcinoma, Non-Small-Cell Lung Cancer, Immunotherapy, Myasthenia Gravis, NivolumabAbstract
Background: Against limited effectiveness of known oncological treatment such as chemio-and radiotherapy or surgery, new ways of treatment, such as for example immunotherapy has developed. Usage of immune checkpoint inhibitors (ICPIs), resulting in overactivation of immune system, may significantly raise efficacy of oncological treatment, but simultaneously predispose to occurrence various autoimmunological health complications. Adverse actions of the therapy may affect multiple organs and systems, with the presented example of immune-related neurological complication, myasthenia gravis. This relatively rare condition may be severe, life-threatening illness.
Case report: We present a case of 66-year-old male patient diagnosted with a large tumor histopathologically assessed as squamous cell carcinoma. Due to ineffectiveness of implemented chemio- and radiotherapy, he was qualified for anti-PD1 immunotherapy with nivolumab. General treatment tolerance was very good with positive antineoplastic effect. Autoimmune hypothyroidism has emerged, therefore levothyroxine therapy has been implemented. After about a year of using immunotherapy, significant weakness and decrease in muscle strength has appeared, subsequently, immunotheraphy-related myasthenia gravis was raised. Improvement in the patient's condition was achieved after initiating pyridostigmine treatment. Cessation of antineoplastic treatment wasn’t necessary, what is unusual.
Conclusions:
Undeniably myastenia gravis may determine serious, life-threatening adverse effect of immunotherapy. Usually requires withdrawal of applied antioncological treatment, and should be treated with immunomodulators, immunosuppressants or intravenous immunoglobulins or plasmaphaeresis, however – as we present- in some cases may be properly cured only with pyridostygmine.
References
Hofmann L, Forschner A, Loquai C, Goldinger SM, Zimmer L, Ugurel S, et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer. 2016 Jun 1;60:190–209.
Zhang X, Schwartz JCD, Guo X, Bhatia S, Cao E, Chen L, et al. Structural and functional analysis of the costimulatory receptor programmed death-1. Immunity. 2004 Mar 1;20(3):337–47.
Dalakas MC. Neurological complications of immune checkpoint inhibitors: what happens when you ‘take the brakes off’ the immune system. Ther Adv Neurol Disord [Internet]. 2018 Jan 14 [cited 2020 Oct 13];11:175628641879986. Available from: http://journals.sagepub.com/doi/10.1177/1756286418799864
Martins F, Sofiya L, Sykiotis GP, Lamine F, Maillard M, Fraga M, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Vol. 16, Nature Reviews Clinical Oncology. Nature Publishing Group; 2019. p. 563–80.
Hua C, Boussemart L, Mateus C, Routier E, Boutros C, Cazenave H, et al. Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. JAMA Dermatology. 2016 Jan 1;152(1):45–51.
Indini A, Di Guardo L, Cimminiello C, Prisciandaro M, Randon G, De Braud F, et al. Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma. J Cancer Res Clin Oncol [Internet]. 2019 Feb 13 [cited 2020 Oct 12];145(2):511–21. Available from: http://link.springer.com/10.1007/s00432-018-2819-x
Xu C, Chen YP, Du XJ, Liu JQ, Huang CL, Chen L, et al. Comparative safety of immune checkpoint inhibitors in cancer: Systematic review and network meta-analysis. BMJ. 2018 Nov 1;363.
Anderson R, Theron AJ, Rapoport BL. Immunopathogenesis of immune checkpoint inhibitor-related adverse events: Roles of the intestinal microbiome and Th17 cells. Vol. 10, Frontiers in Immunology. Frontiers Media S.A.; 2019.
Dalvin LA, Shields CL, Orloff M, Sato T, Shields JA. Checkpoint inhibitor immune therapy. Vol. 38, Retina. Lippincott Williams and Wilkins; 2018. p. 1063–78.
Hu J-R, Florido R, Lipson EJ, Naidoo J, Ardehali R, Tocchetti CG, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors. Cardiovasc Res [Internet]. 2019 Apr 15 [cited 2021 Jun 3];115(5):854–68. Available from: https://academic.oup.com/cardiovascres/article/115/5/854/5304411
Ederhy S, Cautela J, Ancedy Y, Escudier M, Thuny F, Cohen A. Takotsubo-Like Syndrome in Cancer Patients Treated With Immune Checkpoint Inhibitors. JACC Cardiovasc Imaging. 2018 Aug 1;11(8):1187–90.
Zimmer L, Goldinger SM, Hofmann L, Loquai C, Ugurel S, Thomas I, et al. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer. 2016 Jun 1;60:210–25.
Common Terminology Criteria for Adverse Events (CTCAE) | Protocol Development | CTEP [Internet]. [cited 2020 Nov 9]. Available from: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_60
Horta E, Bongiorno C, Ezzeddine M, Neil EC. Neurotoxicity of antibodies in cancer therapy: A review. Vol. 188, Clinical Neurology and Neurosurgery. Elsevier B.V.; 2020.
Kao JC, Liao B, Markovic SN, Klein CJ, Naddaf E, Staff NP, et al. Neurological complications associated with anti–programmed death 1 (PD-1) antibodies. JAMA Neurol. 2017 Oct 1;74(10):1216–22.
Moreira A, Loquai C, Pföhler C, Kähler KC, Knauss S, Heppt M V., et al. Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors. Eur J Cancer. 2019 Jan 1;106:12–23.
Becquart O, Lacotte J, Malissart P, Nadal J, Lesage C, Guillot B, et al. Myasthenia Gravis Induced by Immune Checkpoint Inhibitors. J Immunother. 2019 Oct 1;42(8):309–12.
Gonzalez NL, Puwanant A, Lu A, Marks SM, Živković SA. Myasthenia triggered by immune checkpoint inhibitors: New case and literature review. Neuromuscul Disord. 2017 Mar 1;27(3):266–8.
Suzuki S, Ishikawa N, Konoeda F, Seki N, Fukushima S, Takahashi K, et al. Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology. 2017 Sep 1;89(11):1127–34.
Gilhus NE. Myasthenia Gravis. Longo DL, editor. N Engl J Med [Internet]. 2016 Dec 29 [cited 2020 Nov 5];375(26):2570–81. Available from: http://www.nejm.org/doi/10.1056/NEJMra1602678
Lv Z, Zhong H, Huan X, Song J, Yan C, Zhou L, et al. Predictive Score for In-Hospital Mortality of Myasthenic Crisis: A Retrospective Chinese Cohort Study. Eur Neurol. 2019 Nov 1;81(5–6):287–93.
Huang Y-T, Chen Y-P, Lin W-C, Su W-C, Sun Y-T. Immune Checkpoint Inhibitor-Induced Myasthenia Gravis. Front Neurol [Internet]. 2020 Jul 16 [cited 2020 Nov 4];11:634. Available from: https://www.frontiersin.org/article/10.3389/fneur.2020.00634/full
Makarious D, Horwood K, Coward JIG. Myasthenia gravis: An emerging toxicity of immune checkpoint inhibitors. Vol. 82, European Journal of Cancer. Elsevier Ltd; 2017. p. 128–36.
Lau KHV, Kumar A, Yang IH, Nowak RJ. Exacerbation of myasthenia gravis in a patient with melanoma treated with pembrolizumab. Muscle and Nerve. 2016 Jul 1;54(1):157–61.
Zivelonghi C, Zekeridou A. Neurological complications of immune checkpoint inhibitor cancer immunotherapy. Vol. 424, Journal of the Neurological Sciences. Elsevier B.V.; 2021. p. 117424.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Ewa Tywanek, Katarzyna Jankowska, Agnieszka Zwolak, Wojciech Zgliczyński, Robert Jan Łuczyk
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 95
Number of citations: 0
