Although CAR T-cell therapies have been associated with dramatic clinical responses and high rates of complete remission, they also have unique toxicity profiles, including some life-threatening adverse reactions. Hence, careful monitoring and early identification of these toxicities, as well as prompt intervention, is essential to the management of patients receiving CAR T-cell therapy, a report published in the Clinical Journal of Oncology Nursing has shown.1

First approved by the US Food and Drug Administration (FDA) in 2017, CAR T-cell therapy has provided a very powerful tool for the treatment of a number of B-cell malignancies. Currently, two CAR T-cell therapies, tisagenlecleucel and axicabtagene ciloleucel, have been granted FDA approval. Both are modified autologous T-cell products directed against CD19, a surface antigen overexpressed on malignant B cells.2

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Cytokine release syndrome (CRS) is a common, potentially life-threatening toxicity associated with CAR T-cell therapy that occurs when cytokines, such as tumor necrosis factor alpha, interleukin-2, and interleukin-6, are systemically released in response to the activation and proliferation of CAR T-cells. The hallmark of CRS is high fever, with other possible symptoms including tachycardia, myalgias, and fatigue; organ dysfunction is a possible clinical sequelae.

Median onset of CRS is usually within 2 to 3 days of CAR T-cell infusion, with symptoms typically appearing within 1 to 2 weeks of treatment administration. Grading scales and consensus guidelines have been developed to aid in CRS assessment. Management of CRS includes supportive care and may involve administration of tocilizumab, an interleukin-6 receptor inhibitor, and/or corticosteroids.

CAR T-cell therapy has also been commonly associated with development of neurologic toxicity, also referred to as CAR T-cell–related encephalopathy syndrome and immune effector cell–associated neurologic toxicity syndrome. The pathophysiology of CAR T-cell-related neurotoxicity is less well understood, although elevated cytokine levels and CAR T-cell penetration into the CNS may be involved. Symptoms of CAR T-cell-related neurologic toxicity include decreased attention, disorientation, encephalopathy, anxiety, confusion, delirium, language disturbances, difficulties, aphasia, somnolence, ataxia, weakness, and seizures.

Median onset of symptoms is usually within 1 week of treatment administration, although later onset has been observed. A very high degree of clinical suspicion is necessary to identify neurotoxicity in these patients, and some assessment tools have been tailored for this purpose. Management strategies for neurologic toxicity may include tocilizumab and/or corticosteroids for patients experiencing both CRS and neurotoxicity, or corticosteroids for those with neurologic symptoms unrelated to CRS.

Other potential adverse reactions to CAR T-cell therapy include cytopenias, infection, hypogammaglobulinemia, and tumor lysis syndrome.

Nursing management is critically important to recognizing the potential adverse effects and providing care coordination with timely escalation of care for patients undergoing CAR T-cell therapy.

Reference

1. Anderson K, Latchford T. Associated toxicities: assessment and management related to CAR T-cell therapy. Clin J Oncol Nurs. 2019;23(2):13-19.

2. Lamprecht M, Dansereau C. CAR T-cell therapy: update on the state of the science. Clin J Oncol Nurs. 2019;23(2):6-12.