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Immune-related adverse events of checkpoint inhibitors

Abstract

Cancer immunotherapies have changed the landscape of cancer treatment during the past few decades. Among them, immune checkpoint inhibitors, which target PD-1, PD-L1 and CTLA-4, are increasingly used for certain cancers; however, this increased use has resulted in increased reports of immune-related adverse events (irAEs). These irAEs are unique and are different to those of traditional cancer therapies, and typically have a delayed onset and prolonged duration. IrAEs can involve any organ or system. These effects are frequently low grade and are treatable and reversible; however, some adverse effects can be severe and lead to permanent disorders. Management is primarily based on corticosteroids and other immunomodulatory agents, which should be prescribed carefully to reduce the potential of short-term and long-term complications. Thoughtful management of irAEs is important in optimizing quality of life and long-term outcomes.

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Fig. 1: Mechanism of immune checkpoints and immune checkpoint inhibitors.
Fig. 2: Mechanism of immune-related adverse events.
Fig. 3: Radiological and/or photographical appearance of immune-related adverse events.
Fig. 4: Rate of reactivation/flare of pre-existing autoimmune diseases after immune checkpoint inhibitor therapy.
Fig. 5: Suggested therapeutic algorithm for the organ-by-organ management of irAEs.

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Acknowledgements

This work was supported in part by the Memorial Sloan Kettering Cancer Center (MSKCC) NCI core grant P30 CA008748 and the University of Texas NCI core grant P30 CA016672. The authors thank F. Schettini from IDIBAPS/Hospital Clinic (Barcelona, Spain) for his assistance with the manuscript.

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Introduction (A.F.-C.); Epidemiology (A.P.); Mechanisms/pathophysiology (M.E.S.-A.); Diagnosis, screening and prevention (M.K.C., N.K., M.A.K. and X.M.); Management (J.R.B. and O.L.); Outlook (M.R.-C.); Overview of Primer (M.R.-C.).

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Correspondence to Manuel Ramos-Casals.

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Competing interests

M.R.-C. has received compensation for consulting services and/or speaking activities from Bristol-Myers Squibb and Gilead. J.R.B. has received compensation for consulting services and/or speaking activities from Amgen, AstraZeneca, Bristol-Myers Squibb, Genentech and Merck. M.K.C. declares institutional research support and employment of a family member by Bristol-Myers Squibb and consulting, advisory or speaking compensation from AstraZeneca/MedImmune, Incyte, Moderna and Merck. O.L. has received compensation for consulting services and/or speaking activities from AstraZeneca, Bristol-Myers Squibb France, Incyte, Janssen and MSD, and received research support from Gilead. X.M. has received compensation for consulting services and/or speaking activities from Bristol-Myers Squibb. A.P. has received compensation for consulting services and/or speaking activities from Amgen, Bristol-Myers Squibb, Daiichi Sankyo, Novartis, Oncolytics Biotech, Pfizer, Puma and Roche, and received research support from Boehringer Ingelheim, Nanostring, Novartis and Roche. M.E.S.-A. has received funding for consulting services from AbbVie, Agile Pharmaceuticals, Amag Pharmaceuticals, Eli Lilly and Pfizer unrelated to this topic. All other authors declare no competing interests.

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Ramos-Casals, M., Brahmer, J.R., Callahan, M.K. et al. Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers 6, 38 (2020). https://doi.org/10.1038/s41572-020-0160-6

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