A body temperature reading of lower than 98.6 F is considered normal when obtained from

Immediate Care

After the tisagenlecleucel infusion, the patient receives another 1-hour infusion with normal saline for hydration. The patient may be discharged from the apheresis unit once vital signs are stable but should be reminded to remain within a 1-hour transportation distance from Penn for at least 28 days postinfusion.

Follow-Up Care and Toxicity Management

Two to three follow-up patient appointments occur during the first week postinfusion, and set visits occur weekly thereafter for the next month. Appointments beyond the first month are at the provider's discretion. Triaging patient phone calls and judging AE severity for subsequent patient admission is a challenge for outpatient therapy. From the nurse's perspective, these decisions require exceptional communication across the multidisciplinary team, the patients, and their families. Factors that may inform a provider's decision for admission may include changes in vital signs, severity of symptoms, tumor burden, potential for toxicity, and/or signs of neurotoxicity. For outpatient postinfusion monitoring, patients and caregivers are educated about signs and symptoms of potential serious AEs, given a wallet card that directs them when to seek emergency care, and are instructed to have an oral thermometer (plus a backup) and taught how to use it to monitor for fever. Patients are also instructed to call the oncology call center during business hours and are triaged to the appropriate team, and the treating oncologist or nurse practitioner will contact the patient for additional information. After hours, the general hospital operator pages the treating oncologist, who then instructs the patient to report to the most appropriate location for evaluation based on symptoms.

Fever is an expected AE of tisagenlecleucel therapy and an early indicator of CRS, a potentially life-threatening inflammatory response. Patients are instructed to have two oral thermometers available for postinfusion monitoring and to monitor their temperature at the same time in the morning, afternoon, and evening each day and if they are feeling unwell. Patients with a temperature of 38°C (100.4°F) or higher are evaluated by a physician or APP to exclude infection as the source. Patients with fever will be evaluated in the oncology evaluation center or the hematology-oncology clinic and, depending on severity of symptoms, may be admitted to the hospital.

Cytokine Release Syndrome

CRS is a systemic inflammatory response associated with CAR T-cell therapy and other immunotherapies.11 The severity of CRS can range from mild to life-threatening depending on the magnitude of the immune cell activation. Preparation for the early identification and clear management of CRS is crucial for patient safety. CRS severity is assessed by grade according to easily accessible clinical features. A consensus grading scale for CRS has been published by the American Society for Transplantation and Cellular Therapy (ASTCT), and Penn has adopted the ASTCT CRS grading scale (Table 2).12 CRS is managed according to guidance provided in the Kymriah prescribing information.2 The presentation, onset, and management of other common AEs are shown in Table 3.2,11,13,14

Table 2. ASTCT CRS Grading Scale12

ASTCT, American Society for Transplantation and Cellular Therapy; BiPAP, bilevel positive airway pressure; CPAP, continuous positive airway pressure; CRS, cytokine release syndrome.

Table 3. Anticipated Sequelae and Management After Tisagenlecleucel Infusion2,11,13,14

ASTCT, American Society for Transplantation and Cellular Therapy; ANC, absolute neutrophil count; CRS, cytokine release syndrome; CT, computed tomography; EEG, electroencephalography; LD, lymphodepleting; MRI, magnetic resonance imaging.

Neurological Events

After receiving CAR-T cell therapy, patients may also experience neurological events that may occur concurrent with CRS, after resolution of CRS, or in the absence of CRS. Before infusing tisagenlecleucel in the outpatient setting, patients and caregivers are educated by the APP, a nurse clinical trials coordinator, and a physician about the potential for developing immune effector cell-associated neurotoxicity syndrome (ICANS), which may manifest as altered or decreased consciousness, delirium, confusion, agitation, seizures, difficulty speaking and understanding, and loss of balance. Patients are also given a wallet card that lists the key symptoms of immune effector cell-associated neurotoxicity syndrome and advises them to contact their oncologist or seek emergency care. As indicated, it is often the APP who advises patients when to seek emergency care based on their symptoms. Overall, neurological events are managed based on the underlying pathophysiology. At Penn, neurological symptoms are assessed using the ASTCT consensus grading scale for neurologic toxicity, which uses the immune effector cell-associated encephalopathy (ICE) score to grade neurotoxicity.12 For patients who experience neurological events, such as cognitive changes, encephalopathy, aphasia, or motor disturbances, seizure prophylaxis (such as levetiracetam) may be administered (Table 3). Patients experiencing mild events are observed and monitored closely. In patients with more pronounced neurological symptoms, the treating oncologist may administer steroids (eg, dexamethasone 10-20 mg, every 8-12 hours) until symptoms return to baseline. In the event of concurrent CRS and neurotoxicity, tocilizumab may be appropriate; however, tocilizumab is not approved by the US Food and Drug Administration (FDA) for the treatment of neurological symptoms alone.