CAR T cells are genetically engineered in the laboratory to produce synthetic receptors on the surface of T cells and are then given back to the patient by infusion so they are able to recognize and kill cancer cells while they circulate in the body.
Currently, there are 2 CAR T-cell therapies approved by the FDA: axicabtagene ciloleucel (Yescarta), used to treat relapsed or refractory large B-cell lymphoma in adults; and tisagenlecleucel (Kymriah), for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse, and also for adult patients with relapsed or refractory large B-cell lymphoma.
According to Ms White, there are a number of unique challenges to using CAR T-cell therapy in solid tumors, but the hope is that utilizing other immunotherapies (such as checkpoint inhibitors) in conjunction with CAR T cells will enable them to target these malignancies in the future.
A Navigation Program to Support CAR T-Cell Therapy
The Children’s Hospital of Philadelphia was one of the first centers in the country to offer CAR T-cell therapy by clinical trial. “We were seeing a huge influx of patients from all over the country,” said Ms White at the AONN+ 9th Annual Navigation & Survivorship Conference. “We needed to build a robust support network to make sure we were getting them in the door.” They now have a team comprising 2 nurse navigators, an access coordinator, physicians, nurse practitioners, a social worker, a financial coordinator, and clinical research staff.
Her role as CAR T-cell navigator is heavily focused on patient screening. “Often, these kids have been through years of therapy; they may have been recently diagnosed but had a horrible up-front course,” she said. “We don’t want them getting on a plane unless we really think we can treat them.” After screening comes triaging, followed by care planning: determining next steps for a patient and relaying proactive education to the referring provider.
In a navigator role, emotional and educational support starts immediately. “It’s a new therapy; it’s confusing and scary, and it requires education to start at day 1 and continue throughout long-term follow-up,” she said. “Often, these CAR T cells are living in these patients for the near future. They need to know what that means.”
Other navigator responsibilities include outreach—partnering to make sure all patients have equal access to CAR T-cell therapy—and process evaluation and improvement.
The Screening Process
A navigator must consider a host of factors in the screening process for CAR T-cell therapy. First and foremost, candidates must have the correct disease and the correct target (ie, CD19-positive disease in the setting of a CD19-targeted CAR T-cell trial).
Level of disease control must be determined (is it worsening by the day?) as well as disease location (has it metastasized?), current treatment status (is the patient currently getting chemotherapy?), and the patient’s organ function (will they be able to tolerate the potentially sepsis-like side effects of CAR T-cell therapy?).
Early in the process, the navigator should anticipate whether the cardiology or neurology teams should be involved (does the patient have a history of febrile seizures?). The patient’s activity level should also be assessed, as this is important to understanding their performance status. “If the patient isn’t able to walk through the front door, we have good reason to believe he or she won’t be able to tolerate CAR T therapy,” said Ms White.
The navigator should determine whether insurance coverage will be a barrier to care, and if the patient has a strong support system. “We perform our services outpatient, so we require that our patients come with a caregiver in case of side effects,” she noted.
According to Ms White, a successful referral requires a partnership with the physician or care team that referred the patient to CAR T-cell therapy. “We try not to let people in our door without feeling like this will be a potential therapy for them, and that requires a close partnership,” she said. “And after the patient receives therapy at our site, we send them back to the team they came from, so it’s really important that the team feels like part of the care planning process.”
Principles of Side Effect Management
Common toxicities associated with CAR T-cell therapy include cytokine release syndrome (CRS), neurotoxicity, and B-cell aplasia (low numbers or absence of B cells).
CRS is common, but its severity depends on the patient’s disease burden at the time of treatment. It can be as mild as fatigue or headache or as severe as multiorgan failure. “The most important thing to tell patients and frontline staff is that typically, CRS will present with a fever,” she said. “Families are well educated on fever guidelines.”
Neurotoxicity can present in various forms, from a nonresponsive febrile patient to cerebral edema. For patients with increased risk of neurotoxicity, get the neurology team involved early, she advised. Get baseline MRIs as needed, and start the patient on seizure prophylaxis.
B-cell aplasia is an expected result of successful CD19-specific CAR T-cell treatment and can actually be a useful indicator of ongoing CAR T-cell activity.
“CD19-directed CAR T cells don’t know how to detect a healthy B cell compared to a cancerous one, so they go after all CD19-positive B cells,” she explained. “This results in B-cell aplasia, but we think that’s OK. They come to clinic once a month after, get their IV immunoglobulin, and then they’re on their way.” After 6 months, patients can begin home replacement, which is typically approved by insurance, and should continue replacement therapy as long as they have circulating CAR T cells.
Continue to Educate
According to Ms White, patient education begins at the time of referral to a CAR T-cell therapy center, and it should continue throughout the patient’s acute and chronic follow-up period. Education priorities are dependent on the patient’s diagnosis and type of CAR T-cell therapy received. “As we start to see solid tumor CAR T-cell products come out that target the microenvironment of the disease rather than the disease itself, these are going to require unique management and patient education,” she said. “It will be important to partner with research teams, study teams, trial sponsors, and, ultimately, pharmaceutical companies in order to drive good patient education so we can continue to deliver T-cell therapy in a safe and effective way.”
Finally, patients and families should be exhaustively educated on the early warning signs of CRS onset and should have access to an oncology provider 24 hours a day, 7 days a week.
“It’s so important to review with patients and their families: even if you’re feeling well, even if you’re not neutropenic, it’s so critical to call with a fever,” she emphasized. “It’s the first sign of a CRS storm starting.”