Vol 8, No 3 (2022)
Review paper
Published online: 2022-09-30
Rheumatic manifestations in cancer patients treated with immune checkpoint inhibitors
DOI: 10.5603/RF.2022.0015
Rheumatology Forum 2022;8(3):98-104.
Abstract
Immune checkpoint inhibitors are a breakthrough therapy for oncological patients. These drugs are considered effective in fighting cancer cells by supporting immune system. Their clinical efficancy is well documented however immune-related adverse events caused by drugs are the subject of interest of many research works. It is estimated that 15% to 90% of patients treated by immune checkpoint inhibitors experienced immune-related adverse events including 0,5-13% that require termination of the oncotherapy and provide immunosuppressive agents. The most common rheumatic manifestations of the immune checkpoint inhibitors therapy was arthralgia, myalgia, inflamatory arthritis, myositis. During the treatment, patients also present symptoms of systemic lupus erythematosus, vasculitis or sicca syndrome.
Keywords: rheumatic manifestationsoncological diseasesimmune checkpoint inhibitors
References
- Esfahani K, Meti N, Miller W, et al. Adverse events associated with immune checkpoint inhibitor treatment for cancer. Canadian Medical Association Journal. 2019; 191(2): E40–E46.
- Alsaab HO, Sau S, Alzhrani R, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017; 8: 561.
- Kostine M, Truchetet ME, Schaeverbeke T. Clinical characteristics of rheumatic syndromes associated with checkpoint inhibitors therapy. Rheumatology. 2019; 58(Suppl 7): vii68–vii74.
- Lee KA, Kim HR, Yoon S. Rheumatic complications in cancer patients treated with immune checkpoint inhibitors. Korean J Intern Med. 2019; 34(6): 1197–1209.
- Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12(4): 252–264.
- Kumar V, Chaudhary N, Garg M, et al. Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy. Front Pharmacol. 2017; 8: 49.
- Louthrenoo W, Kasitanon N, Wongthanee A, et al. CTLA-4 polymorphisms in Thai patients with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. Int J Rheum Dis. 2021; 24(11): 1378–1385.
- Gao J, Gai N, Wang Li, et al. Meta-analysis of programmed cell death 1 polymorphisms with systemic lupus erythematosus risk. Oncotarget. 2017; 8(22): 36885–36897.
- Wang J, Yoshida T, Nakaki F, et al. Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes. Proc Natl Acad Sci U S A. 2005; 102(33): 11823–11828.
- Zou Y, Zhang Z, Liu Y, et al. Are programmed cell death 1 gene polymorphisms correlated with susceptibility to rheumatoid arthritis?: A meta-analysis. Medicine (Baltimore). 2017; 96(35): e7805.
- Kostine M, Finckh A, Bingham CO, et al. EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors. Ann Rheum Dis. 2021; 80(1): 36–48.
- Cappelli LC, Gutierrez AK, Bingham CO, et al. Rheumatic and musculoskeletal immune-related adverse events due to immune checkpoint inhibitors: A systematic review of the literature. Arthritis Care Res (Hoboken). 2017; 69(11): 1751–1763.
- Kostine M, Rouxel L, Barnetche T, et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-clinical aspects and relationship with tumour response: A single-centre prospective cohort study. Ann Rheum Dis. 2018; 77(3): 393–398.
- Benfaremo D, Manfredi L, Luchetti MM, et al. Musculoskeletal and rheumatic diseases induced by immune checkpoint inhibitors: A review of the literature. Curr Drug Saf. 2018; 13(3): 150–164.
- Zhong H, Zhou J, Dong X, et al. Rheumatic immune-related adverse events induced by immune checkpoint inhibitors. Asia Pac J Clin Oncol. 2021; 17(3): 178–185.
- Touat M, Maisonobe T, Knauss S. Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer. Neurology. 2018; 91(10): e985–e994.
- Pathak R, Katel A, Massarelli E, et al. Immune checkpoint inhibitor-induced myocarditis with myositis/myasthenia gravis overlap syndrome: a systematic review of cases. Oncologist. 2021; 26(12): 1052–1061.
- Xing Q, Zhang ZW, Lin QH, et al. Myositis-myasthenia gravis overlap syndrome complicated with myasthenia crisis and myocarditis associated with anti-programmed cell death-1 (sintilimab) therapy for lung adenocarcinoma. Ann Transl Med. 2020; 8(5): 250.
- Melissaropoulos K, Klavdianou K, Filippopoulou A, et al. Rheumatic manifestations in patients treated with immune checkpoint inhibitors. Int J Mol Sci. 2020; 21(9): 3389.
- Raschi E, Antonazzo IC, Poluzzi E, et al. Drug-induced systemic lupus erythematosus: should immune checkpoint inhibitors be added to the evolving list? Ann Rheum Dis. 2021; 80(7): e120.
- Fadel F, El Karoui K, Knebelmann B. Anti-CTLA4 antibody-induced lupus nephritis. N Engl J Med. 2009; 361(2): 211–212.
- Shao K, McGettigan S, Elenitsas R, et al. Lupus-like cutaneous reaction following pembrolizumab: An immune-related adverse event associated with anti-PD-1 therapy. J Cutan Pathol. 2018; 45(1): 74–77.
- Liu RC, Sebaratnam DF, Jackett L. Subacute cutaneous lupus erythematosus induced by nivolumab. Australas J Dermatol. 2018; 59(2): e152–e154.
- Comont T, Sibaud V, Mourey L, et al. Immune checkpoint inhibitor-related acral vasculitis. J Immunother Cancer. 2018; 6(1): 120.
- Ramos-Casals M, Maria A, Suárez-Almazor ME, et al. ICIR. Sicca/Sjögren's syndrome triggered by PD-1/PD-L1 checkpoint inhibitors. Data from the International ImmunoCancer Registry (ICIR). Clin Exp Rheumatol. 2019; 37 Suppl 118(3): 114–122.
- Moseley KF, Naidoo J, Bingham CO, et al. Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series. J Immunother Cancer. 2018; 6(1): 104.
- Belkhir R, Burel SLe, Dunogeant L, et al. Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment. Ann Rheum Dis. 2017; 76(10): 1747–1750.
- Kramer R, Zaremba A, Moreira A, et al. Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors. Eur J Cancer. 2019; 106: 12–23.
- Cappelli LC, Gutierrez AK, Baer AN, et al. Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. Ann Rheum Dis. 2017; 76(1): 43–50.
- Michot JM, Fusellier M, Champiat S, et al. Drug-induced lupus erythematosus following immunotherapy with anti-programmed death-(ligand) 1. Ann Rheum Dis. 2019; 78(7): e67.
