• Closely monitor patients daily for ≥7 days following infusion and continue monitoring for ≥4 wk for signs/symptoms of CRS (fever, rigors, tachycardia, hypotension, confusion, delirium, arthralgia, myalgia, headache, dizziness, nausea, vomiting, shortness of breath, wheezing). Evaluate for and treat other causes of fever, hypoxia, and hypotension. Administer pretreatment medications to ↓ risk and immediately evaluate patient for hospitalization at the 1st signs/symptoms of CRS. Monitor with continuous cardiac telemetry and pulse oximetry if suspected. If Grade 1 CRS occurs >72 hr after infusion: Give symptomatic treatment; If Grade 1 CRS occurs <72 hr after infusion: Give tocilizumab 8 mg/kg (max = 800 mg) IV over 1 hr. If Grade 2 CRS (oxygen requirement <40% FiO_₂, hypotension responsive to fluids or low dose of one vasopressor, or Grade 2 organ toxicity) occurs: Give tocilizumab 8 mg/kg IV (max = 800 mg) over 1 hr; if not clinically responsive to IV fluids or supplemental oxygen, repeat tocilizumab every 8 hr as needed (max = 3 doses in 24 hr and total of 4 doses). If improving, discontinue tocilizumab. If no improvement ≤24 hr after starting tocilizumab, manage with corticosteroids according to Grade 3; if improving, taper corticosteroids. If Grade 3 CRS (oxygen requirement >40% FiO₂, hypotension requiring high-dose or multiple vasopressors, Grade 3 organ toxicity, or Grade 4 transaminitis) occurs: Consider performing an echocardiogram to assess cardiac function and provide intensive care supportive therapy. Give tocilizumab as in Grade 2; if improving, discontinue tocilizumab. Administer methylprednisolone 1 mg/kg IV twice daily or dexamethasone 10 mg IV every 6 hr until Grade ≤1; then taper corticosteroids. If improving, manage as Grade 2. If not improving, manage as Grade 4. If Grade 4 CRS (requirement for ventilator support or continuous veno-venous hemodialysis, or Grade 4 organ toxicity excluding transaminitis) occurs: Consider performing an echocardiogram to assess cardiac function and provide intensive care supportive therapy. Give tocilizumab as in Grade 2; if improving, discontinue tocilizumab. Administer methylprednisolone 1000 mg IV once daily for 3 days. If improving, taper corticosteroids, and manage as Grade 3; if not improving, consider alternate immunosuppressants.
• Establish baseline neurological status with immune effector cell-associated encephalopathy (ICE) scores. Monitor for neurologic toxicities, including encephalopathy, aphasia, and seizures closely for 1st 7 days and continue ≥4 wk after treatment. Provide seizure precautions and monitor with continuous cardiac telemetry and pulse oximetry if suspected. Consider nonsedating antiseizure medicines (levetiracetam) for seizure prophylaxis. If Grade 1 neurologic toxicity occurs <72 hr after infusion: Consider dexamethasone 10 mg IV every 12–24 hr for 2–3 days. If Grade 1 neurologic toxicity occurs >72 hr after infusion: Observe patient. If Grade 2 neurologic toxicity occurs: Administer dexamethasone 10 mg IV every 12 hr for 2–3 days. If no improvement after 24 hr or worsening of neurologic toxicity occurs, ↑ dose and/or frequency of dexamethasone up to a max of 20 mg IV every 6 hr. If Grade 3 neurologic toxicity occurs: Administer dexamethasone 10–20 mg IV every 6–12 hr. If no improvement after 24 hr or worsening of neurologic toxicity occurs, ↑ to methylprednisolone 2 mg/kg IV loading dose, followed by 0.5 mg/kg IV every 6 hr; taper within 7 days. If Grade 4 neurologic toxicity occurs: Administer dexamethasone 20 mg IV every 6 hr. If no improvement after 24 hr or worsening of neurologic toxicity, ↑ to high-dose methylprednisolone 1–2 g, repeated every 24 hr if needed; taper as clinically indicated. If cerebral edema suspected with Grades 3 and 4: Consider hyperventilation and hyperosmolar therapy. Give high-dose methylprednisolone (1–2 g; repeat every 24 hr, if needed; taper as clinically indicated) and cyclophosphamide 1.5 g/m².
• Establish baseline measurements of cardiac function by performing a transthoracic echocardiogram or multigated acquisition scan.
• Monitor for hemophagocytic lymphohistiocytosis/macrophage activation syndrome, including fatal and life-threatening reactions.
• Monitor for signs/symptoms of secondary malignancies, including T-cell malignancies (fatigue, unexplained weight loss, persistent pain, sore throat, lymphadenopathy, new lumps or swelling).
• Monitor for signs/symptoms of infection (fever, chills, cough, headache, malaise, flu-like symptoms, dysuria, hematuria, cellulitis, erythematous nonhealing wound) before and after infusion; prophylactic antimicrobials and antiviral medications recommended.
• Monitor for signs/symptoms of hypersensitivity reactions (rash, urticaria, pruritus, flushing, dizziness, vomiting, abdominal pain) and angioedema (swelling of throat, lips, tongue, or face; dyspnea; wheezing; hoarseness). Discontinue immediately and provide supportive care.

Lab Test Considerations:

• Verify negative pregnancy status in women of reproductive potential.
• Monitor CBC with differential after infusions.
• Monitor immunoglobulin levels and B-cell counts monthly after treatment because of risk of B-cell aplasia and hypogammaglobulinemia.
• Perform screening for hepatitis B virus, hepatitis C virus, and HIV before collection of cells for manufacturing.
• Establish baseline markers of CRS to allow for earliest possible recognition and response, including C-reactive protein, ferritin, LDH, CBC, and comprehensive metabolic panel (including magnesium and phosphate). Monitor daily in the inpatient setting following CAR-T cell therapy, adding fibrinogen and uric acid, where required.
• Establish baseline serum troponin and brain natriuretic peptide.