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Cytokine Release Syndrome: The Downside of CAR T-Cell Therapy

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September 8, 2020

Grading CRS Is the First Step in Managing this Side Effect

  • CAR T-cell therapy has produced lasting responses in patients with relapsed or refractory hematologic cancers
  • The rapid release of cytokines can lead to a response known as cytokine release syndrome (CRS)
  • Grade 1 CRS can be treated with supportive medications, while grade 3 patients need to be hospitalized
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Chimeric antigen receptor (CAR) T-cell therapy has had great success thus far, producing lasting responses and even remissions in patients with relapsed or refractory hematologic cancers such as B-cell lymphoma and acute lymphoblastic leukemia (ALL).

However, despite improved oncologic outcomes, the use of CAR T-cell therapy is also associated with multiple toxicities, including several that can be life threatening. The rapid release of inflammatory cytokines can lead to cytokine release syndrome (CRS), producing symptoms like a fever, rapid heart rate, and low blood pressure.

Step one in manging CRS is to ensure the patient is stabilized and then determine the grade. “If it is mild, we call it grade 1,” Dr. Siddhartha Ganguly, deputy director of hematologic malignancies and cellular therapeutics at KU Medical Center, tells SurvivorNet Connect. “Many of the patients stay in grade 1 and we use supportive medications — antipyretics like Tylenol, antibiotics — and they get better. But sometimes, they don’t.”

Once patients reach grade 3, they need treatment in an intensive care unit to manage symptoms related to organ dysfunction. “When cytokine release syndrome advances beyond the supportive measures, then we have to use specific treatment with anti-cytokines, medications that counteract the cytokines,” Dr. Ganguly says. Tocilizumab has become the standard of care for CRS, because of its ability to rapidly reverse symptoms. Corticosteroids are also helpful for managing inflammation.