Immune checkpoint inhibitors (ICI) used in oncology can improve progression-free survival (e.g. 3-5 years1 in non small cell lung cancer) and overall survival in some cancer patients with advanced malignancies. Some cancers can acquire immune checkpoints so that the tumour cells are not recognised by the immune system. Inhibiting the checkpoints therefore enables the tumour cells to be recognised and allows an immune response to be activated against them.2
These therapies can occasionally cause auto-immune attacks on non-cancerous tissue, causing severe and, rarely, fatal adverse events [called immune-related adverse events (irAEs)], especially if not promptly recognized and treated.3
The risk, clinical manifestations, and severity of irAEs is variable across ICI regimen and cancer type, and incidence can range from 15 to 90%.4 IrAEs typically represent a medical emergency, with patients appearing in the emergency department. These adverse events often appear infectious, when in fact they result from the immune toxicity caused by immune checkpoint therapy. IrAEs can occur in any organ system, but adverse events in dermatologic (e.g. rash), gastrointestinal (e.g. diarrhea, colitis), endocrine (e.g. thyroid dysfunction), and respiratory (e.g. pneumonitis) systems are among the most common5,6. High clinical suspicion, timely evaluation and multi-disciplinary management provide the foundation for optimal clinical outcomes4. IrAEs are primarily treated with corticosteroids, which suppress the overactive immune response that is secondary to the treatment. Physicians should be familiar with IrAEs and screen for ICI use for all patients presenting to the ED.
The following notes provide physicians with a guide to the management of IrAEs, based on currently available treatment guidelines. The goal of this program is to assist physicians in rapidly making treatment decisions at crucial points during the management of patients with IrAEs.
- Domagała-Kulawik J. Immune checkpoint inhibitors in non-small cell lung cancer – towards daily practice. Adv Respir Med. 2018;86(3). doi:10.5603/ARM.2018.0022
- Ardolino L, Joshua A. Immune checkpoint inhibitors in malignancy. Aust Prescr. 2019;42(2):62-67. doi:10.18773/austprescr.2019.012
- Esfahani K, Meti N, Miller WH, Hudson M. Adverse events associated with immune checkpoint inhibitor treatment for cancer. CMAJ. 2019;191(2):E40-E46. doi:10.1503/cmaj.180870
- Connolly C, Bambhania K, Naidoo J. Immune-Related Adverse Events: A Case-Based Approach. Front Oncol. 2019;9. doi:10.3389/fonc.2019.00530
- Simmons D, Lang E. The Most Recent Oncologic Emergency: What Emergency Physicians Need to Know About the Potential Complications of Immune Checkpoint Inhibitors. Cureus. October 2017. doi:10.7759/cureus.1774
- Myers G. Immune-related adverse events of immune checkpoint inhibitors: a brief review. Current Oncology. 2018;25(5). doi:10.3747/co.25.4235
- Postow MA, Sidlow R, Hellmann MD. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. New England Journal of Medicine. 2018;378(2):158-168. doi:10.1056/NEJMra1703481
ED: Emergency department
IrAEs: immune-related adverse events
CTLA-4: cytotoxic T-lymphocyte antigen 4
PD-1: Programmed cell death 1
PD-L1: Programmed cell death ligand 1