CAR T-Cell Therapy: Power, Passion, and Tempering the Storm

December 2020 Vol 11, No 12



Chimeric antigen receptor (CAR) T-cell (CAR-T for short) products have the power and the potential to cure, according to Kathleen McDermott, RN, BSN, OCN, BMTCN, from Dana-Farber Cancer Institute in Boston. However, ensuring the success of these treatments in patients with cancer requires vigilant forecasting of their potential toxicities.

“The CAR-T team needs to be prepared to temper these toxicities and to navigate patients safely through any CAR-T storm,” she said at the Oncology Nursing Society Bridge Virtual Conference. “Just as the knowledge of an impending snowstorm allows me to predict and plan, this is also true for the care of the CAR-T patient. Assessing the patient’s medical, social, and environmental conditions, as well as knowing the science and technology behind the CAR-T product, provides the nurse the ability to forecast any potential storms in the patient’s future.”

What Is CAR T-Cell Therapy?

T-cells play a key role in the immune system by attacking viruses, infected/foreign cells, and cancer cells. But in a patient with cancer, the T-cells do not recognize the cancer as a foreign pathogen that should be killed.

CAR T-cells are genetically engineered T-cells that express a specific antibody to a commonly expressed antigen on a malignant cell, allowing them to attack and kill cancer cells. Ms McDermott noted that CAR T-cells are target-specific, not tumor-specific.

“When explaining CAR-T cells, I tell my patients, ‘your T-cells are going to be sent to boot camp to be genetically engineered,’” she said. “They’ll become ‘Super Storm Troopers.’ They’ll be trained to recognize and find the cancer with the addition of more T-cell receptors on their surface and added triggers inside the T-cell to kill the cancer once located.”

According to Ms McDermott, increased ammunition in the form of CAR T-cells is needed to treat certain cancers, such as relapsed/refractory diffuse large B-cell lymphoma. In large retrospective studies, patients with this particular malignancy have demonstrated poor responses to conventional chemotherapy and a dismal prognosis, with a median overall survival of a little over 6 months and a complete remission rate of only about 7%.

“Now enter these genetically engineered CAR-T soldiers,” she said. “They’re different from conventional chemotherapy; they’re dynamic, they migrate, they proliferate, and they differentiate. They respond to their environment in vivo and have persistence.” In pivotal trials of CAR T-cell products, patients with non-Hodgkin lymphoma in whom 2 or more therapies had failed demonstrated a markedly increased median overall survival of about 24 months, with complete response rates of 35% to 40%, she reported.

The CAR T-Cell Climate Zones

According to Ms McDermott, the CAR T-cell process consists of a series of steps, or “climate zones,” including screening/evaluation, apheresis, manufacturing, bridging therapy (to try to decrease and keep the patient’s active disease under control during the manufacturing process), lymphodepletion chemotherapy (to create an optimal environment for the CAR T-cells to expand and proliferate by depleting the patient’s lymphocytes), CAR T-cell infusion, the acute toxicity phase, and finally, long-term monitoring.

In the first climate zone, it is critical that providers screen for baseline conditions, evaluate risks, and provide preemptive education and planning. First, the patient must meet the medical criteria for CAR T-cell therapy, so disease pathology, treatment history, medical history, comorbidities, performance status, demographics, and family and social supports should all be evaluated in an initial assessment. This evaluation should be followed up with education, a critical step in helping to quell patient and family anxieties and establish realistic expectations.

During the apheresis and shipment phase, CAR T-cell centers must ensure the optimal climate for successful manufacturing, beginning by following the manufacturer’s recommended stopping times for previous therapies, including steroids, growth factors, and chemotherapy, and ensuring the patient’s lymphocyte count is high enough, as per the guidelines. “This is critical to make sure the patient comes to the apheresis center ready and in an optimal state to provide good raw material to send to the manufacturer,” she said.

The manufacturing phase includes leukapheresis and shipment to the manufacturer, followed by genetic engineering, T-cell activation, and transduction. The modified T-cells are then expanded and undergo quality testing before the product is shipped back to the treatment center, where the patient will undergo lymphodepletion and infusion of the modified T-cells.

During the actual treatment period when the CAR T-cells are infused, toxicity management begins, starting with avoiding “preventable squalls” by using prophylactic therapies, antiviral regimens and allopurinol to help prevent tumor lysis syndrome, and Keppra for seizure control and prevention, she said.

Acute Toxicities and Monitoring

Ms McDermott warned that providers should anticipate “brewing CAR-T storms,” including cytokine release syndrome (CRS), neurological toxicities, “on-target, off-tumor” side effects related to B-cell aplasia, tumor lysis syndrome, infection risk, and prolonged cytopenia.

To deal with the “cytokine release storm,” interleukin-6 inhibition with tocilizumab and siltuximab are commonly used, in addition to corticosteroids for higher-grade CRS (or if the patient is not responsive to tocilizumab).

The second wave comes in the form of neurotoxicity (also called immune effector cell-associated neurotoxicity syndrome [ICANS]). Early symptoms occur concurrently with CRS symptoms (within the first 5 days), late symptoms begin after CRS symptoms have resolved (characterized by seizures and episodes of confusion), and delayed neurotoxicity occurs at 3 to 4 weeks after infusion, characterized by diminished attention and language disturbance, whereas higher grades of neurotoxicity may progress to severe confusion, aphasia, tremors, seizures, and encephalopathy. But the average onset is around day 6 after infusion and can happen with or without the presence of CRS.

The immune effector cell-associated encephalopathy score is used to grade the severity of neurotoxicity and should be combined with other ICANS assessments, if applicable, to arrive at a patient’s final grade. Recommended treatment for neurotoxicity usually includes steroids. “But with early-grade neurotoxicity, we can just use supportive care without having to treat,” she noted.

CAR T-Cell Aftershocks and Post-Storm Recovery

Up to 30 days postinfusion, patients must stay near a certified CAR T-cell facility. During the first 30 days, patients most commonly complain of extreme fatigue, anorexia, and malaise. “These are symptoms we have all experienced when recovering from the flu,” she said. “Remember this CAR-T immune effect is similar to a flu response, but exponentially higher.”

Caregivers and patients must be informed and educated on any signs and symptoms that should be reported, as well as how to report them. “Patients or a family member must always be able to locate the patient’s wallet ID card so they can present that to any provider if there’s a change in their condition and they end up in an emergency room,” she said. “If there’s a protocol, make sure you understand what needs to be reported. The key to that for the nurse, particularly the nurse at the bedside during the high-risk period, is a good communication plan. You should know who to call and when.”

Postinfusion, patients should be continuously monitored for B-cell aplasia, a form of collateral damage related to treatment. “It’s one of the aftershocks that occurs in about 15% of patients with adult lymphoma, but it can be treated very easily with gamma globulin replacement infusions,” she said. Blood counts should be closely monitored even after the high-risk period and continued after the patient leaves the treatment facility, as hypogammaglobulinemia and cytopenia put patients at a higher risk for infection.

After day 30, the post-storm recovery begins. Fatigue begins to lift, and patients return to their community setting. At this point, the patient’s local care facility should receive a comprehensive handoff from the CAR T-cell facility, inclusive of clear monitoring guidelines, as well as contact numbers for staff at the CAR T-cell facility should the patient have questions or need support.

“Long-term follow-up is required by the FDA for patients who receive genetically modified products, so the CAR-T facility is going to be looking to the local facility for follow-up,” she said. “There should be a good handoff, with clear guidelines for patient care.”

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Last modified: August 10, 2023

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