As of February 2019, only 160 institutions across the United States are certified to administer CAR T-cell therapy, meaning many eligible patients may need to be referred to a treatment center outside of the local ambulatory or community cancer center where they had previously received treatment. The transition from primary oncologist to certified center and back again requires careful coordination to ensure important steps and information aren’t lost.

In their article in the April 2019 supplement to the Clinical Journal of Oncology Nursing, Beaupierre et al. presented an overview of the six phases of CAR T-cell therapy key considerations for referring providers and institutions prior to and following the treatment.

Phase 1: Consultation and Workup

Patients are evaluated for CAR T-cell therapy in three areas: indication and eligibility requirements, psychological stability to proceed to treatment, and insurance or self-pay authorization and logistic requirements, Beaupierre et al. explained. CD19-positive status is confirmed after  having progressed through two lines of systemic therapy, and patients’ physical functioning is assessed, including history and physical, performance status, and baseline lab studies.

Referring providers should understand CAR T-cell therapy eligibility requirements as well as the financial and logistical considerations for treatment. They’re also required to provide a patient’s current records, including diagnostic scans, pathology reports, and history and physical findings.

Phase 2: Leukapheresis

In this phase, patients’ peripheral blood T cells are collected through a catheter and sent to the manufacturer for CAR T-cell processing and production. Depending on the product, a varying target number of cells is needed, but the collection usually takes two to three hours, Beaupierre et al. reported.

As part of the eligibility assessment, referring providers should identify patients’ history of stem cell transplantation, review  current medications, and assess complete blood count (CBC) and vascular access. In some cases, patients cannot have allogenic stem cell transplantation within three months of CAR T-cell therapy. For the leukapheresis process, CBC should show at least 27% hematocrit and 20 × 109/l platelets. If peripheral venous access is compromised, patients will need a temporary dialysis-grade catheter for central venous access.

Phase 3: Bridging

Because CAR T-cell therapy production can take two to six weeks from white blood cell collection to the return of the treatment product, patients with aggressive malignancies may experience symptomatic disease progression before therapy begins. Bridging therapy is used to control disease, debulk the tumor, and maintain performance status without undue toxicity, Beaupierre et al. explained.

For lymphoma, common regimens include IV chemotherapy (e.g., rituximab, gemcitabine, and oxaliplatin), oral chemotherapy (e.g., prednisone, etoposide, procarbazine, and cyclophosphamide), high-dose steroids (e.g., dexamethasone 40 mg for four days), or radiation therapy. For leukemia, regimens are lower-
intensity adaptions of known B-cell acute lymphoblastic leukemia therapies.

Bridging can take place at either the referring or treating center. Patients should be educated about the reason for the therapy and prepared for the transition to the treating institution, if they have not already done so. Explain the collaborative approach to treatment between the two centers to ensure patients understand the continuity of care. 

Phase 4: Lymphodepleting Chemotherapy

If patients received bridging treatment, their cancer should be restaged before beginning lymphodepleting chemotherapy in preparation for CAR T cells, Beaupierre et al. said. Lymphodepleting chemotherapy prepares patients’ bodies by depleting their own T cells to create an optimal environment for the CAR T cells to expand and proliferate. Agents may vary but typically involve fludarabine and cyclophosphamide given over three to four days. If patients are receiving it in the ambulatory setting, they should have a caregiver present 24 hours a day and live within two hours of the treating facility, although some facilities require patients to stay closer (e.g., 30 minutes).

Referring center considerations: This step is conducted at the treating center, so the referring provider should expect to receive updates on a patient’s treatment plan and status.

Phase 5: Infusion and Monitoring

Treating providers will need to monitor patients for the two most commonly observed acute toxicities following CAR T-cell therapy: cytokine release syndrome and neurologic toxicities. Cytokine release syndrome is marked by high fevers, tachycardia, hypotension, and hypoxia, and it may progress to multiorgan failure. Neurotoxicities involve encephalopathic syndrome characterized by confusion, tremor, delirium, seizures, and cerebral edema, potentially leading to coma, but most are temporary and reversible.

Pancytopenia is expected, and delayed cytopenia (past day 28) occurs in 24% of patients, Beaupierre et al. reported. Supportive care includes transfusions and intermittent granulocyte–colony-stimulating factor injections (e.g., filgrastim); however, the manufacturer does not recommend these for cytopenias within three weeks of CAR T-cell therapy.

Use of anti-CD19 CAR T cells may result in B-cell aplasia, Beaupierre et al. said. Patients will be immunocompromised and at risk for frequent infections and may require monthly IV immunoglobulin G supplementation.

Restaging scans are performed 30–90 days post infusion and every three months for the first two years, Beaupierre et al. said. Response rates and durable remissions are high with CAR T-cell therapy, but patients with acute lymphoblastic leukemia are at greater risk for early relapse and may need consolidative allogeneic stem cell transplantation.

The referring provider will continue to receive reports and treatment plans during this phase to prepare for long-term monitoring.

Phase 6: Handoff and Long-Term Follow-Up

Patients require close follow-up to monitor for late effects of therapy, such as prolonged cytopenias, increased risk of infection, and delayed neurologic toxicities, Beaupierre et al. explained. Use of acyclovir for antiviral prophylaxis for one year and trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia for six months is recommended. 

Continued collaboration between treating and referring providers is critical at this step. Treating providers will determine follow-up with restaging, and referring providers will recommend follow-up frequency between staging. 

Educate patients about the risk of persistent or long-term toxicities and share examples of side effects (e.g., fatigue, dizziness, coordination problems). Reinforce the education that patients should not drive or operate heavy machinery for eight weeks after CAR T-cell infusion. Educate patients with B-cell aplasia that they are at higher risk for community-acquired infections, and monitor peripheral blood counts for transfusion requirements and growth factor support. 

Referring providers should also watch for signs of disease recurrence, such as unexplained fevers or chills, new pain, or lymphadenopathy, which would warrant reimaging scans to rule out relapse.

For more information about collaborative management for patients receiving CAR T-cell therapy across treating centers and referring community providers, refer to the full article by Beaupierre et al.

Questions regarding the information presented in this article should be directed to the Clinical Journal of Oncology Nursing editor at Photocopying of this article for educational purposes and group discussion is permitted.