What is cytokine release syndrome (CRS) caused by chimeric antigen receptor (CAR) T-cell therapy and how is it treated?

Updated: May 04, 2018
  • Author: Sameh Gaballa, MD, MS; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Answer

CRS results when activated CAR T-cells rapidly release large amounts of cytokines, including interleukin (IL)-6 and interferon γ, into the bloodstream. Onset of signs and symptoms typically occurs days after the CAR T-cell infusion (occasionally, weeks later), coinciding with the maximal expansion of the CAR T-cell population in the patient. The incidence and severity of CRS appear to be greater in patients with large tumor burdens, presumably because those patients experience higher levels of T-cell activation. [22]

Clinically, CRS typically presents as fever (which may exceed 40.0° C) and flulike illness (eg, fever, nausea, fatigue, headache, myalgias, malaise). With higher grades of CRS, patients develop hypotension and organ toxicity (eg, acute respiratory distress syndrome, renal failure, liver failure, cardiac dysfunction, disseminated intravascular coagulation, and encephalopathy). [2, 22]

Therapy for CRS begins with symptomatic treatment for mild manifestations. Supplemental oxygen is indicated for patients with respiratory symptoms; ventilator support may be necessary for the most severe cases. Hypotension is treated with fluids and vasopressors. [22]

Tocilizumab, which blocks IL-6 activity, has become standard therapy for severe CRS. Fever and hypotension often resolve within a few hours after administration of tocilizumab, allowing patients to be weaned off vasopressors and other supportive care measures. Patients with incomplete responses may require continued aggressive support for several days. In patients whose condition does not improve or stabilize within 24 hours after receiving tocilizumab, a second dose of tocilizumab or administration of an immunosuppressant (eg, a corticosteroid) should be considered. [22]


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