CAR T-Cell Therapy Use Requires Schooling of Adverse Event Recognition and Management

Due to the potency of CAR T-cell therapies and the associated adverse events (AEs) that can to arise in patients receiving this type of treatment, such as cytokine release syndrome (CRS) and neurotoxicity, oncology nurses need to be educated on how to best identify and manage these AEs.

In a presentation during the 5th Annual School of Nursing Oncology, Kelly Garvin, BSN, RN, OCN, Department of Malignant Hematology, H. Lee Moffit Cancer Center, highlighted the methods that nurses can use to discuss the utility and efficacy of CAR T-cell therapy with patients, as well as how to recognize and stay on top of these associated AEs to ensure treatment can be continued.

Explaining CAR T-cell Therapy to Patients

The word chimeric has mythological roots. It once referred to a creature with the body of a dragon, the head of a turtle, and the tail of a serpent, according to Garvin. It is also defined as a tissue containing two distinct populations. Understanding this etymology helps demystify the concept of CAR T-cell therapy for patients.

CAR T cells are T lymphocyte cells that have been “reprogrammed” to target the antigens on the surface of a cancer cell (such as CD19 or BCMA). The CAR T cells then proceed to attack the cancer cells as if they were an infection.

The Process

The first step, according to Garvin, is to identify who would be an appropriate candidate to receive CAR T-cell therapy. Vital organ testing needs to then be done on the candidate. The next step is to withdrawal the whole blood from the patient, separate the T cells, and then return the rest of the blood to the patients.

The T lymphocyte cells are then sent to a special lab which uses genetic engineering to make the CARs. The T cells are then infused with the CARs and then that infusion undergoes a rigorous testing process. Currently, there are 5 approved products on the market (tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, idecabtagene vicleucel) and each of these has a different clinical testing process.

Finally, before the patient receives the CAR T cells, they receive a lymphodepleting combination of fludarabine and cyclophosphamide. This process, according to Garvin, helps reduce the presence of other lymphocytes so that the reinjected T cells have more space to grow. Garvin recommended nurses give those patients two days of rest between the lymphodepletion and the administration of the CAR T cells. The cells, once returned to the body, multiply, and remain to provide surveillance.

“Once those T cells come in contact with the bad cell, the result can be very dramatic. They become activated, they start looking for the cancer cells, they start killing the cancer cells, and so the result can be dramatic and explosive,” Garvin explained.

Recognizing the Unique Adverse Events

The two main AEs that are associated with the use of CAR T -cell therapies are cytokine release syndrome (CRS) and neurotoxic events such as immune effector cell-associated neurotoxicity syndrome (ICANS). CRS is typically the first observed AE and appears within the first week after treatment. While CRS is a natural event, the T-cell stimulation accelerates it and results in a potentially lethal increase in inflammatory cytokines. This, in turn, can lead to fever, edema, hypotension and organ disfunction, explained Garvin.

The other common AE oncology nurses should be aware of, according to Garvin, is neurotoxicity. On average, neurotoxic events occur 4 days after treatment. It usually follows CRS although it can be concurrent. Neurotoxicity is often biphasic and is usually marked by symptoms such headaches, aphasia, seizure, tremor, confusion, decreased LOC, and a difficulty with words.

“I remember once asking a patient a question and she just looked at me with a blank stare in her eyes, she didn't really seem to understand what I was saying,” she recalled. “[This patient is] normally chatty. Now, she doesn’t know what I'm what I'm asking her.”

Nurses should also be aware of other common AEs associated with the use of CAR T-cell therapies including prolonged cytopenias, B-cell aplasia and hypogammaglobinemia and hemophagocytic lymphohistiocytosis/macrophage activation syndrome, Garvin noted.

Remaining Vigilant in Identifying AEs

One of the easiest things nurses can do to remain vigilant in looking for AEs, she explained, is to take vital signs every 4 hours.

One of the first signs of CRS is a high fever. If a patient begins to show signs of a temperature spike, Garvin said her team is immediately ready. Other signs that point to the potential presence of CRS include fever, chills, hypotension, tachycardia, and hypoxia. If a symptom appears, the team’s first response is to administer antifebrile medications, as well as two liters of nasal canula.

While CRS can be life-threatening, it can usually be managed through early intervention. Sometimes, patients who have received CAR T cells are briefly sent to the ICU if their hypotension becomes unmanageable. But they are usually able to return, she said.

If the CRS (grade 3 or 4) becomes too difficult to manage with the regular interventions, then Garvin said her team will usually try tocilizumab.

“Tocilizumab is the therapy for severe CRS,” she said. “I've seen it reverse patient symptoms within hours. It's really dramatic. And if that doesn't work, sometimes we will use steroids.”

Just as with CRS, early detection is also necessary to effectively manage neurotoxicity. Garvin suggested that oncology nurses asking patients some of the following questions every 4 hours:

1. Do you have a headache?
2. What is your name?
3. Where are you?
4. What day is today?

In addition, nurses can ask their patients to perform the following tasks:

• Raise their eyebrows,
• Stick their tongue out and wiggle it back and forth,
• Lift their arms straight into the air or straight out in front of themself,
• Identify an object such as a clock or button, or
• Write a coherent sentence such as “blue is my favorite color.”

If a patient is unable to complete these tasks, the nurse should suspect that neurotoxicity is brewing and react by calling for a neuro consult, she explained. The next action, according to Garvin, is to respond with seizure precautions. She requires that patients take nothing by mouth, and she lowers the bed to the lowest threshold. In addition, she said they administer levetiracetam to their patients because their seizure threshold is lower. They then increase the dose if the patient has a preexisting seizure risk.

The Future of CAR T-cell Therapies

Although CAR T cell therapies are associated with some potent AEs, the treatment continues to offer patients whose disease has not responded to various lines of treatment hope, according to Garvin. In coming years, Garvin said she hopes to see many changes in the landscape of CAR T-cell treatment, including allogeneic CAR T products and the use of CAR T-cell therapy for other diseases.

Reference

1. Garvin KL. CAR-T therapy nursing considerations; patient education & toxicity management. Presented at: 5th Annual School of Nursing Oncology Live; August 6-7, 2021; virtual.