Identifying and Treating Cytokine Release Syndrome

Chimeric antigen receptor (CAR) T-cell therapy is an immunotherapeutic approach that utilizes gene transfer to reprogram the patient’s T-cells to recognize and eliminate cancerous cells by targeting and interacting with tumor-associated antigens. CAR T-cell therapy has yielded promising  results in hematologic malignancies, including acute lymphoblastic leukemia, chronic lymphoblastic leukemia, and multiple myeloma, by targeting CD19; B-cell non-Hodgkin lymphoma by targeting CD19 or CD20; and acute myeloid leukemia by targeting Lewis Y antigen or CD33.

This powerful immunomodulating agent with the ability to elicit durable antitumor responses can also elicit severe toxicities. The most common adverse event following CAR T-cell infusion is immune activation, also known as cytokine release syndrome (CRS). CRS occurs with the expansion of adoptive transferred T-cells, and is characterized by immune activation and the release of inflammatory cytokines. Clinical complications of CRS include fatigue, high fever, myalgia, nausea, anorexia, hepatic failure, renal impairment, capillary leak, cardiac dysfunction, tachycardia/hypotension, and disseminated intravascular coagulation.

Studies have shown that the degree of CRS is directly associated with tumor burden at the time of infusion. Patients with a high disease burden at the time of CAR T-cell infusion experience severe CRS, specifically grade ≥3 organ toxicity that is potentially life-threatening and requires aggressive clinical intervention. It is therefore imperative that nurses recognize these toxicities to help reduce CRS-related deaths.

A literature review of CRS was undertaken. The review showed that CRS was graded on a 1-to-5 scale. Mild CRS symptoms, such as myalgia and fever, received a grade 1. Moderate CRS symptoms, requiring intravenous fluids, received a grade 2. Severe CRS symptoms received a grade 3, and CRS symptoms resulting in the need for a ventilator received a grade 4. A grade 5 CRS symptom would be death. The literature review also showed that circulating cytokine levels could be used as a biomarker for diagnosis; however, this poses some limitations.

If a patient experiences CRS during therapy, treatment should be stopped immediately. Tocilizumab, an FDA-approved drug for rheumatoid arthritis, has been used effectively in patients experiencing severe or life-threatening CRS. If there is no improvement after the first tocilizumab infusion, a second dose and corticosteroids should be considered.

As adoptively transferred T-cells expand into different hematologic malignancies and solid tumors, there is a significant need for CRS treatment algorithms. Educating nurses, patients, and caregivers on how to promptly recognize CRS can help prevent life-threatening complications.  

Miller V, et al. ONS Abstract 452.
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Last modified: May 5, 2017