Immune checkpoint inhibitors-related neuromyopathy_West China Medical Journal

Authors：

ZHONG Qingling ^1,2 , ZENG Li ^1,2 ,  TAN Song ^1,2

1. Department of Neurology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, P. R. China;
2. School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P. R. China;

Corresponding author：

TAN Song, Email: 153620904@qq.com

Keywords：

Immune checkpoint inhibitors; Myasthenia gravis; Myositis; Peripheral neuropathy

DOI：

10.7507/1002-0179.202003528

Video：

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In recent years, immune checkpoint inhibitors have begun to be used in targeted cancer therapy. Despite the favorable results in terms of oncological outcomes, these treatments have been associated with a variety of immune-related adverse events. Neuromuscular disease is more common among adverse events involving the nervous system. With the increasing use of immune checkpoint inhibitors, the early recognition and treatment of neuromuscular immune-related adverse events are very important. In this review, we are focused on the epidemiology, pathogenesis, clinical manifestations, evaluation, diagnosis, and treatment of neuromuscular diseases (including peripheral neuropathy, myasthenia gravis, and myositis) caused by immune checkpoint inhibitors, aiming to provide a theoretical basis for improving the diagnosis and treatment ability of users of immune checkpoint inhibitors for such neuromuscular diseases and reducing the disability rate and mortality rate caused by immune checkpoint inhibitors.

Citation： ZHONG Qingling, ZENG Li, TAN Song. Immune checkpoint inhibitors-related neuromyopathy. West China Medical Journal, 2020, 35(6): 734-737. doi: 10.7507/1002-0179.202003528 Copy

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2.	Spain L, Walls G, Julve M, et al. Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. Ann Oncol, 2017, 28(2): 377-385.
3.	Touat M, Talmasov D, Ricard D, et al. Neurological toxicities associated with immune-checkpoint inhibitors. Curr Opin Neurol, 2017, 30(6): 659-668.
4.	Psimaras D, Velasco R, Birzu C, et al. Immune checkpoint inhibitors-induced neuromuscular toxicity: from pathogenesis to treatment. J Peripher Nerv Syst, 2019, 24(Suppl 2): S74-S85.
5.	Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med, 2016, 375(19): 1856-1867.
6.	Pan PC, Haggiagi A. Neurologic immune-related adverse events associated with immune checkpoint inhibition. Curr Oncol Rep, 2019, 21(12): 108.
7.	Kao JC, Liao B, Markovic SN, et al. Neurological complications associated with anti-programmed death 1 (PD-1) antibodies. JAMA Neurol, 2017, 74(10): 1216-1222.
8.	Dalakas MC. Neurological complications of immune checkpoint inhibitors: what happens when you “take the brakes off” the immune system. Ther Adv Neurol Disord, 2018, 11: 1-9.
9.	Kao JC, Brickshawana A, Liewluck T. Neuromuscular complications of programmed cell death-1 (PD-1) inhibitors. Curr Neurol Neurosci Rep, 2018, 18(10): 63.
10.	Chen X, Haggiagi A, Tzatha E, et al. Electrophysiological findings in immune checkpoint inhibitor-related peripheral neuropathy. Clin Neurophysiol, 2019, 130(8): 1440-1445.
11.	Shirai T, Sano T, Kamijo F, et al. Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma. Jpn J Clin Oncol, 2016, 46(1): 86-88.
12.	Nishijima TF, Shachar SS, Nyrop KA, et al. Safety and tolerability of PD-1/PD-L1 inhibitors compared with chemotherapy in patients with advanced cancer: a meta-analysis. Oncologist, 2017, 22(4): 470-479.
13.	Luo W, Wang Z, Tian P, et al. Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. J Cancer Res Clin Oncol, 2018, 144(10): 1851-1859.
14.	Psimaras D. Neuromuscular complications of immune checkpoint inhibitors. Presse Med, 2018, 47(11/12 Pt 2): e253-e259.
15.	Thompson JA, Schneider BJ, Brahmer J, et al. Management of immunotherapy-related toxicities, version 1.2019. J Natl Compr Canc Netw, 2019, 17(3): 255-289.
16.	Touat M, Maisonobe T, Knauss S, et al. Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer. Neurology, 2018, 91(10): e985-e994.
17.	Chen JH, Lee KY, Hu CJ, et al. Coexisting myasthenia gravis, myositis, and polyneuropathy induced by ipilimumab and nivolumab in a patient with non-small-cell lung cancer: a case report and literature review. Medicine (Baltimore), 2017, 96(50): e9262.
18.	Liewluck T, Kao JC, Mauermann ML. PD-1 inhibitor-associated myopathies: emerging immune-mediated myopathies. J Immunother, 2018, 41(4): 208-211.
19.	Seki M, Uruha A, Ohnuki Y, et al. Inflammatory myopathy associated with PD-1 inhibitors. J Autoimmun, 2019, 100: 105-113.
20.	Bilen MA, Subudhi SK, Gao J, et al. Acute rhabdomyolysis with severe polymyositis following ipilimumab nivolumab treatment in a cancer patient with elevated anti-striated muscle antibody. Immunother Cancer, 2016, 4(1): 36.
21.	Anquetil C, Salem JE, Lebrun-Vignes B, et al. Immune checkpoint inhibitor-associated myositis: expanding the spectrum of cardiac complications of the immunotherapy revolution. Circulation, 2018, 138(7): 743-745.
22.	Mammen AL, Rajan A, Pak K, et al. Pre-existing antiacetylcholine receptor autoantibodies and B cell lymphopaenia are associated with the development of myositis in patients with thymoma treated with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand 1. Ann Rheum Dis, 2019, 78(1): 150-152.
23.	Vermeulen L, Depuydt CE, Weckx P, et al. Myositis as a neuromuscular complication of immune checkpoint inhibitors. Acta Neurol Belg, 2020, 120(2): 355-364.
24.	Day JA, Limaye V. Immune-mediated necrotising myopathy:a critical review of current concepts. Semin Arthritis Rheum, 2019, 49(3): 420-429.
25.	Wang Y, Zhou S, Yang F, et al. Treatment-related adverse events of PD-1 and PD-L1 inhibitors in clinical trials: a systematic review and meta-analysis. JAMA Oncol, 2019, 5(7): 1008-1019.
26.	Suzuki S, Ishikawa N, Konoeda F, et al. Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology, 2017, 89(11): 1127-1134.
27.	Hu JR, Florido R, Lipson EJ, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors. Cardiovasc Res, 2019, 115(5): 854-868.
28.	Shah M, Tayar JH, Abdel-Wahab N, et al. Myositis as an adverse event of immune checkpoint blockade for cancer therapy. Semin Arthritis Rheum, 2019, 48(4): 736-740.

1. 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.
2. Spain L, Walls G, Julve M, et al. Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. Ann Oncol, 2017, 28(2): 377-385.
3. Touat M, Talmasov D, Ricard D, et al. Neurological toxicities associated with immune-checkpoint inhibitors. Curr Opin Neurol, 2017, 30(6): 659-668.
4. Psimaras D, Velasco R, Birzu C, et al. Immune checkpoint inhibitors-induced neuromuscular toxicity: from pathogenesis to treatment. J Peripher Nerv Syst, 2019, 24(Suppl 2): S74-S85.
5. Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med, 2016, 375(19): 1856-1867.
6. Pan PC, Haggiagi A. Neurologic immune-related adverse events associated with immune checkpoint inhibition. Curr Oncol Rep, 2019, 21(12): 108.
7. Kao JC, Liao B, Markovic SN, et al. Neurological complications associated with anti-programmed death 1 (PD-1) antibodies. JAMA Neurol, 2017, 74(10): 1216-1222.
8. Dalakas MC. Neurological complications of immune checkpoint inhibitors: what happens when you “take the brakes off” the immune system. Ther Adv Neurol Disord, 2018, 11: 1-9.
9. Kao JC, Brickshawana A, Liewluck T. Neuromuscular complications of programmed cell death-1 (PD-1) inhibitors. Curr Neurol Neurosci Rep, 2018, 18(10): 63.
10. Chen X, Haggiagi A, Tzatha E, et al. Electrophysiological findings in immune checkpoint inhibitor-related peripheral neuropathy. Clin Neurophysiol, 2019, 130(8): 1440-1445.
11. Shirai T, Sano T, Kamijo F, et al. Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma. Jpn J Clin Oncol, 2016, 46(1): 86-88.
12. Nishijima TF, Shachar SS, Nyrop KA, et al. Safety and tolerability of PD-1/PD-L1 inhibitors compared with chemotherapy in patients with advanced cancer: a meta-analysis. Oncologist, 2017, 22(4): 470-479.
13. Luo W, Wang Z, Tian P, et al. Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. J Cancer Res Clin Oncol, 2018, 144(10): 1851-1859.
14. Psimaras D. Neuromuscular complications of immune checkpoint inhibitors. Presse Med, 2018, 47(11/12 Pt 2): e253-e259.
15. Thompson JA, Schneider BJ, Brahmer J, et al. Management of immunotherapy-related toxicities, version 1.2019. J Natl Compr Canc Netw, 2019, 17(3): 255-289.
16. Touat M, Maisonobe T, Knauss S, et al. Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer. Neurology, 2018, 91(10): e985-e994.
17. Chen JH, Lee KY, Hu CJ, et al. Coexisting myasthenia gravis, myositis, and polyneuropathy induced by ipilimumab and nivolumab in a patient with non-small-cell lung cancer: a case report and literature review. Medicine (Baltimore), 2017, 96(50): e9262.
18. Liewluck T, Kao JC, Mauermann ML. PD-1 inhibitor-associated myopathies: emerging immune-mediated myopathies. J Immunother, 2018, 41(4): 208-211.
19. Seki M, Uruha A, Ohnuki Y, et al. Inflammatory myopathy associated with PD-1 inhibitors. J Autoimmun, 2019, 100: 105-113.
20. Bilen MA, Subudhi SK, Gao J, et al. Acute rhabdomyolysis with severe polymyositis following ipilimumab nivolumab treatment in a cancer patient with elevated anti-striated muscle antibody. Immunother Cancer, 2016, 4(1): 36.
21. Anquetil C, Salem JE, Lebrun-Vignes B, et al. Immune checkpoint inhibitor-associated myositis: expanding the spectrum of cardiac complications of the immunotherapy revolution. Circulation, 2018, 138(7): 743-745.
22. Mammen AL, Rajan A, Pak K, et al. Pre-existing antiacetylcholine receptor autoantibodies and B cell lymphopaenia are associated with the development of myositis in patients with thymoma treated with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand 1. Ann Rheum Dis, 2019, 78(1): 150-152.
23. Vermeulen L, Depuydt CE, Weckx P, et al. Myositis as a neuromuscular complication of immune checkpoint inhibitors. Acta Neurol Belg, 2020, 120(2): 355-364.
24. Day JA, Limaye V. Immune-mediated necrotising myopathy:a critical review of current concepts. Semin Arthritis Rheum, 2019, 49(3): 420-429.
25. Wang Y, Zhou S, Yang F, et al. Treatment-related adverse events of PD-1 and PD-L1 inhibitors in clinical trials: a systematic review and meta-analysis. JAMA Oncol, 2019, 5(7): 1008-1019.
26. Suzuki S, Ishikawa N, Konoeda F, et al. Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology, 2017, 89(11): 1127-1134.
27. Hu JR, Florido R, Lipson EJ, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors. Cardiovasc Res, 2019, 115(5): 854-868.
28. Shah M, Tayar JH, Abdel-Wahab N, et al. Myositis as an adverse event of immune checkpoint blockade for cancer therapy. Semin Arthritis Rheum, 2019, 48(4): 736-740.

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