A Body of Evidence Helps Nurses Manage CAR T-Cell Therapy Toxicities
When chimeric antigen receptor (CAR) T-cell therapies were first approved for cancer in 2017, nurses didn’t have years of clinical practice experience with the treatment to understand its full scope of nursing implications yet. Now that nearly five years have passed—and new CAR T-cell therapies have been approved, bringing the total number of treatments to five as well—oncology nurses and nurse scientists have built a robust knowledge base.
In an article in the June 2021 issue of the Clinical Journal of Oncology Nursing, Baer gave an overview of information in the current literature about nursing management of patients receiving CAR T-cell therapy, including standard operating procedures, monitoring recommendations, and toxicity interventions.
How Today’s CAR T Cells Fight Cancer
All of the currently approved CAR T-cell therapies are for the relapsed or refractory setting, Baer explained. All are considered autologous products, which are made from the patient’s own cells. The first four U.S. Food and Drug Administration-approved therapies (i.e., tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel) act against the CD19 antigen, which is expressed in many types of lymphoma and leukemia. The most recent approval, idecabtagene vicleucel, targets the B-cell maturation antigen in multiple myeloma.
CAR T cells work quickly once they’re infused, Baer said. Because cancer cell death is so rapid, patients may experience a bevy of toxicities such as tumor lysis syndrome, cytokine release syndrome (CRS), or immune effector cell–associated neurotoxicity syndrome (ICANS). All are considered oncologic emergencies and require immediate intervention.
Tumor Lysis Syndrome
Tumor lysis syndrome occurs when tumor cells release their contents (e.g., potassium, phosphate, nucleic acid) into the patient’s bloodstream during treatment. Symptoms include:
- Renal: oliguria, anuria, urine crystals, flank pain
- Cardiac: electrocardiogram changes, dysrhythmias, sudden death
- Gastrointestinal: nausea, vomiting, diarrhea, anorexia
- Neuromuscular: cramps, tetany, confusion
By monitoring patients’ laboratory values for hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia, oncology nurses can identify tumor lysis syndrome early and provide prompt management. Although the best treatment is prevention with allopurinol starting one to two days before CAR T-cell infusion, management strategies consist of supportive care (e.g., hydration, loop diuretics, electrolyte replacement), use of allopurinol or rasburicase (or sodium bicarbonate if rasburicase is unavailable), and hemodialysis.
Cytokine Release Syndrome
Rapid cell death also releases cytokines into a patient’s body; when they get to a level that overwhelms the kidneys, CRS (sometimes called cytokine storm) can occur, Baer said. Symptoms typically develop two to five days after infusion and include high fevers, hypotension, hypoxia, and tachycardia.
Prompt recognition and accurate grading guide clinicians in managing CRS for the best outcomes. The American Society for Transplantation and Cellular Therapy (ASTCT) grading system is available online.
Recommended management, based on CRS grading and severity, involves:
- Low: IV fluids and acetaminophen
- Moderate: antipyretics, low-flow oxygen therapy, and vasopressors
- Moderate to severe: high-flow oxygen therapy, anticytokine therapy (e.g., tocilizumab), corticosteroids, and mechanical ventilation
Immune Effector Cell–Associated Neurotoxicity Syndrome
Because research is still emerging about ICANS, clinical practice has a limited understanding of what triggers it, its mechanism, and optimal interventions, Baer explained. What we do know is that oncology nurses must be vigilant about monitoring patients for neurologic effects. ICANS typically develops four to seven days after CAR T-cell infusions, and symptoms can range from fine hand tremors to seizures.
The ASTCT grading system for CRS also grades ICANS, using a patient’s immune effector cell–associated encephalopathy (ICE) score. ICE assesses the patient’s orientation by confirming that they can state their name, location, and the date, as well as their ability to think logically.
ICANS treatment is either corticosteroids alone or with antiepileptics for seizures. Patients with higher-grade toxicity should be referred to neurology and be considered for a lumbar puncture to rule out infection or cerebral edema.
Other Adverse Events
Patients may also experience neutropenia or thrombocytopenia, Baer said. Neutropenia presents as a decreased neutrophil count on complete blood count (CBC) with differential lab studies. Treatment involves the use of granulocyte–colony-stimulating factor, prophylactic microbial coverage, and educating patients on infection prevention.
Thrombocytopenia is evident as decreased platelet counts on CBC lab studies and managed by discontinuing pharmacologic venous thromboembolism prophylaxis. Patients may require platelet transfusions if their platelets are below threshold. Oncology nurses should teach patients with thrombocytopenia about minimizing risk of bleeding, including using a soft toothbrush and not flossing.
Implications for Nursing Practice
Oncology nurses are often a patient with cancer’s most regular provider and are in the best position to regularly monitor patients for CAR T-cell–related toxicities, enabling early identification and quick intervention to achieve the best outcomes. Any change in a patient’s neurologic status, vital signs, or general condition should be reported immediately, Baer said.
Nurses administering CAR T-cell therapies require additional training in Risk Evaluation and Mitigation Strategy and how to respond to and manage the treatment’s adverse events. Many of the CAR T-cell manufacturers provide training programs before approving an institution for administration. Additionally, all providers involved in CAR T-cell treatment should have access to an appropriate grading system (currently ASTCT), which can be incorporated into the electronic health record.
Baer also said that institutions should develop protocols for adverse events to guide nurses and facilitate care. A sample protocol is included in a table in the Clinical Journal of Oncology Nursing article.
For more information about the latest evidence for managing CAR T-cell therapy toxicities, refer to Baer’s full article.