Optimal management of immune-related adverse events resulting from treatment with immune checkpoint inhibitors: a review and update
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Over the last two decades, molecular-targeted agents have become mainstream treatment for many types of malignancies and have improved the overall survival of patients. However, most patients eventually develop resistance to these targeted therapies. Recently, immunotherapies such as immune checkpoint inhibitors have revolutionized the treatment paradigm for many types of malignancies. Immune checkpoint inhibitors have been approved for treatment of melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, Hodgkin’s lymphoma, bladder cancer and gastric cancer. However, oncologists have been faced with immune-related adverse events caused by immune checkpoint inhibitors; these are generally mild but can be fatal in some cases. Because immune checkpoint inhibitors have distinct toxicity profiles from those of chemotherapy or targeted therapy, many oncologists are not familiar with the principles for optimal management of immune-related adverse events, which require early recognition and appropriate treatment without delay. To achieve this, oncologists must educate patients and health-care workers, develop checklists of appropriate tests for immune-related adverse events and collaborate closely with organ specialists. Clinical questions that remain include whether immune checkpoint inhibitors should be administered to patients with autoimmune disease and whether patients for whom immune-related adverse events lead to delays in immunotherapy should be retreated. In addition, the predicted use of combination immunotherapies in the near future means that oncologists will face a higher incidence and severity of immune-related adverse events. This review provides an overview of the optimal management of immune-related adverse events attributed to immune checkpoint inhibitors.
KeywordsImmune-related adverse events Immune checkpoint inhibitor Organ specialists Corticosteroid Immunomodulatory/immunosuppressive agents
Complaince with ethical standards
Conflict of interest
None of the authors of this study declared conflict of interest.
- 12.Rosenberg JE, Hoffman-Censits J, Powles T et al (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387:1909–1920CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Kang YK, Boku N, Satoh T et al (2017) Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390(10111):2461–2471CrossRefPubMedGoogle Scholar
- 20.Di Giacomo AM, Danielli R, Guidoboni M et al (2009) Therapeutic efficacy of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with metastatic melanoma unresponsive to prior systemic treatments: clinical and immunological evidence from three patient cases. Cancer Immunol Immunother 58(8):1297–1306CrossRefPubMedGoogle Scholar
- 50.Bristol-Meyers Squibb: Yervoy (ipilimumab): Immune-mediated adverse reaction management guide. http://www.hcp.yervoy.com/servlet/servlet.FileDownload?file=00Pi000000PI1ZVEA1. Accessed 6 Mar 2018
- 51.Horvat TZ, Adel NG, Dang T-O et al (2015) Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at memorial sloan kettering cancer center. J Clin Oncol 33(28):3193–3198CrossRefPubMedPubMedCentralGoogle Scholar
- 58.Weinstock C, Singh H, Maher VE et al (2017) FDA analysis of patients with baseline autoimmune diseases treated with PD-1/PD-L1 immunotherapy agents. J Clin Oncol. https://doi.org/10.1200/JCO.2017.35.15_suppl.3018
- 59.Leonardi GC, Gainor JF, Azimi RS et al (2017) Use of PD-1 pathway inhibitors among patients with non-small cell lung cancer (NSCLC) and preexisting autoimmune disorders. J Clin Oncol. https://doi.org/10.1200/JCO.2017.35.15_suppl.9081
- 61.Santini FC, Rizvi H, Wilkins O et al (2017) Safety of retreatment with immunotherapy after immune-related toxicity in patients with lung cancers treated with anti-PD(L)-1 therapy. J Clin Oncol. https://doi.org/10.1200/JCO.2017.35.15_suppl.9012