Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance

Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs. Immune-checkpoint inhibitors (ICIs) have dramatically improved the survival of patients with certain forms of cancer; however, these agents also have adverse effects that are often quite different to those of more traditional cancer therapies. In this Review, the authors describe the epidemiology, treatment and management of the various immune-related adverse events that can occur in patients receiving ICIs. Key points The frequency of immune-related adverse events (irAEs) is dependent on the agents used, exposure time and the administered dose but also on the patient’s intrinsic risk factors; conversely, the timing of appearance is often dictated by the affected organ systems. High-risk patients receiving immune-checkpoint inhibitors (ICIs) should be regularly monitored for treatment-related complications by specialized multidisciplinary teams, ideally using a personalized surveillance strategy. The application of formal contraindications to the use of ICIs among patients with a high risk of irAEs is not supported by well-founded scientific evidence. In patients with severe and/or steroid-refractory irAEs, a biopsy sample should be obtained and investigated for infiltrating immune cells in order to enable the selectio