Get Smart on CAR-T – Spoon Feed Version

July 9, 2020

Written by Clay Smith

Spoon Feed
We need to know about the adverse effects of CAR-T therapy – how to recognize and treat it emergently. Here is your guide.

Why does this matter?
Chimeric antigen receptor T-cell (CAR-T) therapy involves using a patient’s own genetically engineered T-cells to attack tumor tissue. The problem is, it sometimes causes too much inflammation and collateral damage. Does this seem like a bad idea, or is it just me? Anyway, here is what you need to know about CAR-T.

Don’t get run over by the CAR-T

• CAR-T is used for B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, or multiple myeloma.

• The two main dangerous side effects are cytokine release syndrome (CRS) and neurotoxicity, both of which are fairly common. Almost all body systems may experience adverse effects. See figure.

• CRS looks like sepsis, with fever and multi-organ failure or dysfunction.

  • Step 1: Call oncology. There is a balance – inflammation kills the tumor; too much inflammation kills the patient.

  • It occurs early, usually in the first week after therapy and may last 2 weeks.

  • Other illnesses like sepsis, adrenal insufficiency, or thyrotoxicosis must be considered and empirically treated.

  • CRS is treated by supporting failing organs (vasopressors, oxygen, fluid, ventilation as needed). Tocilizumab (anti-IL-6R) is used in severe cases. Dexamethasone is second line. Most need the ICU.

• Neurotoxicity may occur with or without CRS.

  • Step 1: Call oncology and neurology.

  • Onset is often within the first week, may last 3 weeks, and may coincide with CRS.

  • It consists of altered mental status, headache, difficulty speaking, anxiety, delirium, frank encephalopathy, and may cause seizure or stroke-like symptoms.

  • Some have frontal release, hypertonia, memory loss, or other odd neurological changes.

  • MRI can usually differentiate stroke vs neurotoxicity.

  • We have to work up all the other bad things that may cause strange neurological symptoms.

  • Treat with high-dose dexamethasone. Refer back to step 1. Tocilizumab alone won’t help.

  • Use anticonvulsants, airway protection, etc. to support them.

Source
Management of Chimeric Antigen Receptor (CAR) T-Cell Toxicities: A Review and Guideline for Emergency Providers. J Emerg Med. 2020 May 27. pii: S0736-4679(20)30352-8. doi: 10.1016/j.jemermed.2020.04.021. [Epub ahead of print]

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