Abstract
Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmable cell death protein 1 (PD-1)/PD-L1 have shown antitumor activity in cancers such as melanoma, non-small cell lung cancer, renal cell carcinoma, and urothelial cancer. Certain checkpoint inhibitors have been approved for use in Canada, and are becoming a mainstay in the treatment of melanoma and other malignancies. These drugs have a unique side effect profile and are known to cause immune-related adverse events (irAEs). These adverse events often appear to originate from an infectious etiology, when in fact they result from the enhanced immune response caused by immune checkpoint therapy. IrAEs are primarily treated with corticosteroids, which suppress the overactive immune response that is secondary to the treatment. IrAEs can occur in any organ system, but adverse events in the skin, gastrointestinal, endocrine, and pulmonary systems are among the most common. As an emergency physician, one must be familiar with these drugs and their adverse events in order to identify patients presenting with irAE and treat them accordingly. This paper provides a brief introduction to immune checkpoint inhibitors, discusses the most common irAEs relevant to emergency physicians, and gives suggestions on how to manage patients presenting to the emergency department (ED) suffering from irAEs.
Highlights
BackgroundImmune checkpoint inhibitors are novel cancer therapeutics that enhance the anti-tumor immune response to various malignancies
A pooled study of nivolumab monotherapy found that, 85% of immune-related adverse events (irAEs) began within the first 16 weeks of therapy, they can occur more than a year after initiating treatment [19]
Immune checkpoint inhibitors have shown promise in the treatment of multiple malignancies. These drugs are becoming more prevalent, and their increased use will result in more patients presenting to the emergency department (ED) suffering from irAE
Summary
Immune checkpoint inhibitors are novel cancer therapeutics that enhance the anti-tumor immune response to various malignancies. Most instances of skin irAE will be less-severe grade 1-2 rashes (Table 3), and these patients will likely not present to the ED If they do, they can continue their immune checkpoint therapy, and be treated symptomatically with topical corticosteroids (e.g. betamethasone 0.1%) and oral antihistamines as needed. With grade 3-4 rashes, immune checkpoint therapy should be delayed, 1-2 mg/kg/day IV methylprednisolone (or oral equivalent) should be administered, a dermatology consult should be scheduled, and the patient may need to be admitted to the hospital depending on the severity of the irAE. It is important to still consider other causes for gastrointestinal symptoms in patients on immune checkpoint inhibitors, such as infection or progression of the patient’s underlying malignancy If these causes are ruled out, symptoms should be managed as irAEs. Grade 1 diarrhea should be managed symptomatically with rehydration and antimotility agents. These patients may require prophylactic antibiotics, bronchoscopy, and/or lung biopsy [21,22]
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