Chimeric antigen receptor T-cell (CAR T-cell) therapy is an exciting but complex novel form of immunotherapy with multiple potential toxicities that nurses must be prepared to recognize and manage, Misty Lamprecht, MS, APRN-CNS, AOCN®, BMTCN®, of the Ohio State University Comprehensive Cancer Center – James in Columbus said during a session on Saturday, April 13, 2019, at the ONS 44th Annual Congress in Anaheim, CA. Lamprecht’s copresenter was Yi Lin, MD, PhD, of the Mayo Clinic Cancer Center in Rochester, MN.
What Is CAR T-Cell Therapy?
In CAR T-cell therapy, T cells isolated from a patient are genetically engineered to express a CAR that recognizes tumor-specific antigens. When injected back into the patient, the CAR T cells induce cell death.
To date, the U.S. Food and Drug Administration has approved two CAR T-cell therapies, one for the treatment of aggressive, relapsed, or refractory B-cell acute lymphocytic leukemia in children or young adults and two for aggressive, relapsed, or refractory B-cell non-Hodgkin lymphoma in adults. Both target the CD19 receptor found on the cell surface in hematologic malignancies. Many clinical trials are currently underway to test CAR T-cell therapies in both hematologic and solid tumors.
Although CAR T-cell therapy is currently being administered only at select centers, patients may be transferred to other institutions for post-treatment follow-up. For this reason, nurses must be able to recognize and manage the associated potential toxicities.
Immune-Related Adverse Events
Cytokine release syndrome (CRS) and neurotoxicity are the two most common severe complications of CAR T-cell therapy requiring prompt, intense medical management. In January 2019 the American Society for Blood and Marrow Transplantation published new consensus guidelines for grading the severity of these complications.
CRS symptoms of fever, nausea, vomiting, diarrhea, hypotension, tachycardia, hypoxia, tachypnea, and rash typically occur 1–14 days after cell infusion, with peak incidence in days 2–7. Most patients experience mild symptoms that can be managed with supportive care in the hospital or, occasionally, on an outpatient basis.
CRS complications may also include a transient decrease in cardiac ejection fraction or stroke volume, renal dysfunction reversible with dialysis, hepatic transaminitis, and acute respiratory distress syndrome. Disseminated intravascular coagulation with clinical bleeding and low or undetectable fibrinogen may occur in severe CRS and may require blood-product support.
Neurotoxicity symptoms may include delirium, encephalopathy, incontinence, seizures, tremors, and paralysis. The onset may be biphasic, with symptoms often occurring concurrently with fever or sedating medication during phase 1 (days 0–5). Phase 2 (after day 5) begins after CRS symptoms have subsided. Seizures may occur as late as the third or fourth week post infusion. Symptoms are generally reversible and typically last two to four days but may occur for a few weeks. A full neurologic workup is appropriate to rule out other etiologies.
Roughly one third to one half of patients in CAR T-cell therapy trials experienced bacterial, viral, or fungal, infections, of which up to one third were grade 3 or higher in severity. Other toxicities that may occur include infusion-related hypersensitivity reactions, prolonged cytopenia, and hypogammaglobulinemia.