Common immune-related adverse reactions of immune checkpoint inhibitors and their management

Abstract

Abstract:

At present, immune checkpoint inhibitors (ICIs) are widely used in clinical, and the common adverse reactions include adverse reactions of skin, gastrointestinal tract, endocrine and liver. Adverse reactions to the lungs and heart are relatively rare, but can be fatal. Systemic steroid therapy is the main treatment for immune related adverse events (irAEs). If there is no response to steroid therapy, an immunomodulator may be considered. Understanding the incidence, pathogenesis, common types and treatment strategies of irAEs can provide theoretical basis for the safe application of ICIs in clinical practice.

Key words:Neoplasms,Immune checkpoint inhibitor,Immune related adverse events,Treatment strategy

Li Hui, Yang Yu. Common immune-related adverse reactions of immune checkpoint inhibitors and their management[J]. Journal of International Oncology, 2021, 48(2): 105-108.

References17

[1]	Inno A, Metro G, Bironzo P, et al. Pathogenesis, clinical manifestations and management of immune checkpoint inhibitors toxicity[J]. Tumori, 2017,103(5):405-421. DOI: 10.5301/tj.5000625. doi:10.5301/tj.5000625pmid:28497847
[2]	Zhou X, Yao Z, Yang H, et al. Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis[J]. BMC Med, 2020,18(1):87. DOI: 10.1186/s12916-020-01549-2. doi:10.1186/s12916-020-01549-2pmid:32306958
[3]	Byrne EH, Fisher DE. Immune and molecular correlates in melanoma treated with immune checkpoint blockade[J]. Cancer, 2017,123(S11):2143-2153. DOI: 10.1002/cncr.30444. doi:10.1002/cncr.30444pmid:28543699
[4]	Kimbara S, Fujiwara Y, Iwama S, et al. Association of antithyroglo-bulin antibodies with the development of thyroid dysfunction induced by nivolumab[J]. Cancer Sci, 2018,109(11):3583-3590. DOI: 10.1111/cas.13800. doi:10.1111/cas.13800pmid:30230649
[5]	Iwama S, De Remigis A, Callahan MK, et al. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody[J]. Sci Transl Med, 2014,6(230):230ra45. DOI: 10.1126/scitranslmed.3008002. doi:10.1126/scitranslmed.3008002pmid:24695685
[6]	Baban B, Liu JY, Qin X, et al. Upregulation of programmed death-1 and its ligand in cardiac injury models: interaction with GADD153[J]. PLoS One, 2015,10(4):e0124059. DOI: 10.1371/journal.pone.0124059. doi:10.1371/journal.pone.0124059pmid:25902191
[7]	Weber JS, Hodi FS, Wolchok JD, et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma[J]. J Clin Oncol, 2017,35(7):785-792. DOI: 10.1200/JCO.2015.66.1389. doi:10.1200/JCO.2015.66.1389pmid:28068177
[8]	Belum VR, Benhuri B, Postow MA, et al. Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor[J]. Eur J Cancer, 2016,60:12-25. DOI: 10.1016/j.ejca.2016.02.010. doi:10.1016/j.ejca.2016.02.010pmid:27043866
[9]	Naidoo J, Schindler K, Querfeld C, et al. Autoimmune bullous skin disorders with immune checkpoint inhibitors targeting PD-1 and PD-L1[J]. Cancer Immunol Res, 2016,4(5):383-389. DOI: 10.1158/2326-6066.CIR-15-0123. doi:10.1158/2326-6066.CIR-15-0123pmid:26928461
[10]	Freeman-Keller M, Kim Y, Cronin H, et al. Nivolumab in resected and unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes[J]. Clin Cancer Res, 2016,22(4):886-894. DOI: 10.1158/1078-0432.CCR-15-1136. doi:10.1158/1078-0432.CCR-15-1136pmid:26446948
[11]	Lacouture ME, Wolchok JD, Yosipovitch G, et al. Ipilimumab in patients with cancer and the management of dermatologic adverse events[J]. J Am Acad Dermatol, 2014,71(1):161-169. DOI: 10.1016/j.jaad.2014.02.035. doi:10.1016/j.jaad.2014.02.035
[12]	Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination[J]. Nat Rev Clin Oncol, 2016,13(8):473-486. DOI: 10.1038/nrclinonc.2016.58. doi:10.1038/nrclinonc.2016.58pmid:27141885
[13]	Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006)[J]. Lancet, 2017,390(10105):1853-1862. DOI: 10. 1016/S0140-6736(17)31601-X. pmid:28822576
[14]	De Velasco G, Je Y, Bossé D, et al. Comprehensive meta-analysis of key immune-related adverse events from CTLA-4 and PD-1/PD-L1 inhibitors in cancer patients[J]. Cancer Immunol Res, 2017,5(4):312-318. DOI: 10.1158/2326-6066.CIR-16-0237. doi:10.1158/2326-6066.CIR-16-0237pmid:28246107
[15]	Geukes Foppen MH, Rozeman EA, van Wilpe S, et al. Immune checkpoint inhibition-related colitis: symptoms, endoscopic features, histology and response to management[J]. ESMO Open, 2018,3(1):e000278. DOI: 10.1136/esmoopen-2017-000278. doi:10.1136/esmoopen-2017-000278pmid:29387476
[16]	Rajha E, Chaftari P, Kamal M, et al. Gastrointestinal adverse events associated with immune checkpoint inhibitor therapy[J]. Gastroenterol Rep (Oxf), 2019,8(1):25-30. DOI: 10.1093/gastro/goz065.
[17]	Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma[J]. N Engl J Med, 2015,372(26):2521-2532. DOI: 10.1056/NEJMoa1503093. doi:10.1056/NEJMoa1503093pmid:25891173