Episode 200: Immune Checkpoint Inhibitors


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Sep 02 2024 13 mins   66




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.





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