Immune Checkpoint Inhibitors

We discuss a new class of medications, Immune Checkpoint Inhibitors, and their side effects.

Hosts:
Avir Mitra, MD
Brian Gilberti, MD

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Show Notes

Overview of Immune Checkpoint Inhibitors (ICIs)

• ICIs are a relatively new class of oncologic drugs that have revolutionized cancer treatment.
• Unlike chemotherapy, ICIs help the immune system develop memory against cancer cells and adapt as the cancer mutates.
• Since their release in 2011, ICIs have expanded to 83 indications for 17 different cancers, with approximately 230,000 patients using them.

Mechanism of Action

• Cancer cells can evade the immune system by binding to T cell receptors that downregulate the immune response.
• ICIs work by blocking these receptors or ligands, preventing the downregulation and allowing T cells to proliferate and attack cancer cells.
• Common ICIs

Risks and Toxicities of ICIs

• ICIs can lead to autoimmune attacks on healthy cells due to immune system upregulation.
• Immune-related adverse effects (irAEs) include colitis, pneumonitis, dermatitis, hepatitis, and endocrine issues (e.g., hypothyroid, hypocortisolemia, hypophysitis).
• These toxicities can present as infections, making diagnosis challenging in the emergency room.

Management of ICI Toxicities in the ER

• Diagnosis: Look for signs that mimic infections (e.g., cough and fever in pneumonitis).
• Diagnostic Imaging in pneumonitis: If CXR is normal but suspicion is high, consider CT scans to differentiate conditions like pneumonitis from other issues such as malignancy-associated pleural effusion or acute pulmonary embolism.
• Treatment: The primary treatment for irAEs is steroids (e.g., prednisone 1 mg/kg). Start steroids early and hold the ICI to manage symptoms effectively and increase the likelihood of resuming ICI therapy later.
• Consider using antibiotics in combination with steroids if there is uncertainty about whether symptoms are due to infection or ICI toxicity.
• Coordinate care with the patient’s oncologist if possible

Disposition Decisions

• Patient disposition (admit vs. discharge) should depend on clinical presentation and severity.
• Coordination with oncology is crucial; they are often comfortable with starting steroids even if there is a potential infection.
• Patients can be discharged if symptoms are mild, but sicker patients with more complex presentations may require admission.

Take-Home Points

• ICIs are a new class of cancer drugs that effectively target cancer cells but come with unique immune-related toxicities.
• Diagnosing irAEs can be challenging due to symptom overlap with infections.
• The cornerstone of treatment is early administration of steroids and temporarily holding the ICI.
• Close collaboration with oncology teams is essential for optimal patient management.