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Immune-related adverse events of checkpoint inhibitors

Nature Reviews Disease Primers volume 6, Article number: 38 (2020) Cite this article

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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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Authors and Affiliations

  1. Department of Autoimmune Diseases, ICMiD, Barcelona, Spain

    Manuel Ramos-Casals

  2. Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona, Spain

    Manuel Ramos-Casals & Alejandra Flores-Chávez

  3. Department of Medicine, University of Barcelona, Hospital Clínic, Barcelona, Spain

    Manuel Ramos-Casals

  4. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

    Julie R. Brahmer

  5. Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Margaret K. Callahan & Niamh Keegan

  6. Weill Cornell Medical College, New York, NY, USA

    Margaret K. Callahan

  7. Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Margaret K. Callahan

  8. Lupus Clinic, Rheumatology Department, Dubai Hospital, Dubai, UAE

    Munther A. Khamashta

  9. APHP Médecine Interne/Immunologie Clinique, Hôpital Bicêtre, Paris, France

    Olivier Lambotte

  10. Université Paris-Saclay, INSERM U1184, CEA, Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Fontenay-aux-Roses and Le Kremlin-Bicêtre, Paris, France

    Olivier Lambotte

  11. Université Paris-Saclay, INSERM, CEA, Centre de recherche en Immunologie des infections virales et des maladies auto-immunes; AP-HP. Université Paris-Saclay, Hôpital Bicêtre, Rheumatology Department, Le Kremlin Bicêtre, Paris, France

    Xavier Mariette

  12. Translational Genomic and Targeted Therapeutics in Solid Tumors, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Aleix Prat

  13. Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain

    Aleix Prat

  14. Section of Rheumatology/Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Maria E. Suárez-Almazor

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  1. Manuel Ramos-Casals
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  4. Alejandra Flores-Chávez
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Contributions

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.).

Corresponding author

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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