The Case of the CAR T-Cell Toxicity Test
Wilson was diagnosed with B-cell lymphoma three days after his 63rd birthday. He underwent chimeric antigen receptor (CAR) T-cell therapy after his disease failed to respond to two lines of systemic chemotherapy.
On day 8 following CAR T-cell therapy, his nurse Becky notices a deterioration in Wilson’s handwriting. She also sees him hesitate when she asks him what hospital he is in and the day of the week, both questions he easily answered the day before. Wilson tells Becky he didn’t sleep well and is just tired.
What Would You Do?
Treating refractory B-cell lymphoma with CAR T-cell therapy (genetically altered T cells trained to recognize and attack certain tumor antigens) shows great promise. However, two conditions—cytokine release syndrome (CRS) and CAR T-cell–related encephalopathy syndrome (CRES)—must be recognized and treated early to reduce the risk of treatment-related morbidity and mortality. Both CRS and CRES are often fatal (https://doi.org/10.1038/nrclinonc.2017.148) if not identified and treated at the earliest opportunity.
CRS: A low-grade fever (38°C), hypotension (systolic blood pressure less than 90 mmHg), and hypoxia (room air arterial blood gas less than 90%) are early signs of CRS. Grade 1 CRS is treated with supportive care, hydration, and close monitoring.Grade 2 is treated with tocilizumab with or without corticosteroids. Grade 3 and 4 CRS require continuous monitoring and aggressive management (http://www.esmo.org/Oncology-News/Assessment-Grading-and-Management-of-Acute-Toxicities-From-CAR-T-Cell-Therapy) in an intensive care unit.
CRES: The initial signs of CRES may be less obvious than CRS; therefore, oncology nurses must judiciously monitor patients for any decline in cognition or other brain-related tasks such as handwriting and counting. When CRES is suspected, nursing interventions include (https://doi.org/10.1038/nrclinonc.2017.148) reporting to the healthcare team and withholding oral intake of food and medications until a detailed neurologic assessment is performed. Progressive signs of CRES include delirium and seizure activity.
Researchers from multiple institutions formed the CAR T-Cell Therapy–Associated TOXicity (CARTOX) Working Group with the goal of developing criteria for monitoring, grading, and treating CAR T-related side effects. The group created a 10-question neurologic assessment (see Figure 1) and recommended using the questions to assess (https://doi.org/10.1038/nrclinonc.2017.148) patients’ neurologic function daily, or more frequently if neurologic impairment is suspected.
Wilson scored an 8 out of 10 on the CARTOX-10. Vigilant IV hydration, aspiration precautions, and more frequent neurologic assessments are initiated because of Becky’s quick identification of neurologic changes.