Novel uses of complement inhibitors in myasthenia gravis-Two case reports.
complement inhibitors
eculizumab
immune check-point inhibitors
myasthenia gravis
pembrolizumab
ravulizumab
Journal
Muscle & nerve
ISSN: 1097-4598
Titre abrégé: Muscle Nerve
Pays: United States
ID NLM: 7803146
Informations de publication
Date de publication:
11 Jan 2024
11 Jan 2024
Historique:
revised:
26
12
2023
received:
25
10
2023
accepted:
29
12
2023
medline:
11
1
2024
pubmed:
11
1
2024
entrez:
11
1
2024
Statut:
aheadofprint
Résumé
Myasthenia gravis (MG) is a rare, life-threatening immune-related adverse effect (irAE) of immune checkpoint inhibitor (ICI) treatment. C5-complement inhibitors are effective treatments for acetylcholine receptor antibody (AChR ab) positive generalized MG. We describe the use of eculizumab/ravulizumab in two patients with MG receiving concomitant pembrolizumab. This was a retrospective review of two medical records. Patient 1: An 80-year-old male with recurrent, non-muscle invasive transitional cell carcinoma of the bladder developed ICI-induced AChR ab positive MG (ICI-MG), myositis, and myocarditis 2 weeks after the first dose of pembrolizumab. Myositis responded to corticosteroids. MG responded to eculizumab, followed by ravulizumab. He died of metastatic cancer 8 months later. Patient 2: A 58-year-old male had refractory thymoma-associated AChR ab-positive MG, which responded to eculizumab. He developed metastatic Merkel cell cancer necessitating pembrolizumab. MG remained stable on eculizumab. He had no irAEs for 22 months, with positron emission tomographic resolution of cancer. He then developed mild, indolent retinal vasculitis, which responded to prednisone. Discontinuation of pembrolizumab for 5 months resulted in cancer recurrence; pembrolizumab was resumed with peri-infusion pulse prednisone. MG remained stable and he continues eculizumab. In the first patient, eculizumab, followed by ravulizumab, improved ICI-MG. In the second patient, eculizumab treatment may have had a prophylactic effect on the development of ICI-induced irAEs. The effect of complement inhibition on cancer outcomes of ICI therapy is unknown. A possible biologic basis for complement inhibitors in reducing irAEs of ICI, especially in the presence of underlying autoimmune disease, merits evaluation.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 Wiley Periodicals LLC.
Références
van der Heide V, Humblin E, Vaidya A, Kamphorst AO. Advancing beyond the twists and turns of T cell exhaustion in cancer. Sci Transl Med. 2022;14(670):eabo4997.
Hude I, Sasse S, Engert A, Brockelmann PJ. The emerging role of immune checkpoint inhibition in malignant lymphoma. Haematologica. 2017;102(1):30-42.
Marin-Acevedo JA, Kimbrough EO, Lou Y. Next generation of immune checkpoint inhibitors and beyond. J Hematol Oncol. 2021;14(1):45.
Abdel-Wahab N, Shah M, Lopez-Olivo MA, Suarez-Almazor ME. Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease. Ann Intern Med. 2018;169(2):133-134.
Huang YT, Chen YP, Lin WC, Su WC, Sun YT. Immune checkpoint inhibitor-induced myasthenia gravis. Front Neurol. 2020;11:634.
Marco C, Simo M, Alemany M, et al. Myasthenia gravis induced by immune checkpoint inhibitors: an emerging neurotoxicity in neuro-oncology practice: case series. J Clin Med. 2022;12(1):130.
Villagran-Garcia M, Velasco R. Neurotoxicity and safety of the rechallenge of immune checkpoint inhibitors: a growing issue in neuro-oncology practice. Neurol Sci. 2022;43(4):2339-2361.
Johansen A, Christensen SJ, Scheie D, Hojgaard JLS, Kondziella D. Neuromuscular adverse events associated with anti-PD-1 monoclonal antibodies: systematic review. Neurology. 2019;92(14):663-674.
Pathak R, Katel A, Massarelli E, Villaflor VM, Sun V, Salgia R. Immune checkpoint inhibitor-induced myocarditis with myositis/myasthenia gravis overlap syndrome: a systematic review of cases. Oncologist. 2021;26(12):1052-1061.
Schneider BJ, Naidoo J, Santomasso BD, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol. 2021;39(36):4073-4126.
Campbell M, Rodriguez-Hernandez A, Rizvi Z, Swerdloff M, Zakin E, Faktorovich S. Efgartigimod for pembrolizumab-induced myasthenia gravis refractory to standard therapy (P1-8.006). Neurology. 2023;100(17):2319.
Nelke C, Pawlitzki M, Kerkhoff R, et al. Immune checkpoint inhibition-related myasthenia-myositis-myocarditis responsive to complement blockade. Neurol Neuroimmunol Neuroinflamm. 2024;11(1):e200177.
Howard JF Jr, Bresch S, Genge A, et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023;22(5):395-406.
Howard JF Jr, Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol. 2017;16(12):976-986.
Hofstadt-van Oy U, Stankovic S, Kelbel C, et al. Complement inhibition initiated recovery of a severe myasthenic crisis with COVID-19. J Neurol. 2021;268(9):3125-3128.
Strano CMM, Sorrenti B, Bosco L, Falzone YM, Fazio R, Filippi M. Eculizumab as a fast-acting rescue therapy in a refractory myasthenic crisis: a case report. J Neurol. 2022;269(11):6152-6154.
Vinciguerra C, Bevilacqua L, Toriello A, et al. Starting eculizumab as rescue therapy in refractory myasthenic crisis. Neurol Sci. 2023;44(10):3707-3709.
Yeo CJJ, Pleitez MY. Eculizumab in refractory myasthenic crisis. Muscle Nerve. 2018;58(2):E13-E15.
Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for Management of Myasthenia Gravis: 2020 update. Neurology. 2021;96(3):114-122.
Reyes A, Mohanty A, Pharaon R, Massarelli E. Association between immunosuppressive therapy utilized in the treatment of autoimmune disease or transplant and cancer progression. Biomedicine. 2022;11(1):99.
Bruera S, Suarez-Almazor ME. The effects of glucocorticoids and immunosuppressants on cancer outcomes in checkpoint inhibitor therapy. Front Oncol. 2022;12:928390.
Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology. 2016;87(4):419-425.
Moradi LA, Clark CA, Schneider CS, Deshane AS, Dobelbower MC. Durable metastatic melanoma remission following pembrolizumab and radiotherapy: a case report of prophylactic immunosuppression in a patient with myasthenia gravis and immune-mediated colitis. Front Immunol. 2021;12:788499.
Nguyen BH, Kuo J, Budiman A, Christie H, Ali S. Two cases of clinical myasthenia gravis associated with pembrolizumab use in responding melanoma patients. Melanoma Res. 2017;27(2):152-154.
Guidon AC. Lambert-Eaton myasthenic syndrome, botulism, and immune checkpoint inhibitor-related myasthenia gravis. Continuum (Minneap Minn). 2019;25(6):1785-1806.
Ueda H, Howson JM, Esposito L, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003;423(6939):506-511.
Kuehn HS, Ouyang W, Lo B, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science. 2014;345(6204):1623-1627.
Chuang WY, Strobel P, Gold R, et al. A CTLA4-high genotype is associated with myasthenia gravis in thymoma patients. Ann Neurol. 2005;58(4):644-648.
Sun L, Meng Y, Xie Y, et al. CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population. PloS One. 2014;9(7):e101986.
Wang XB, Pirskanen R, Giscombe R, Lefvert AK. Two SNPs in the promoter region of the CTLA-4 gene affect binding of transcription factors and are associated with human myasthenia gravis. J Intern Med. 2008;263(1):61-69.