• Closely monitor patients for 1st 7 days following infusion and continue ≥4 wk after treatment 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. Monitor with continuous cardiac telemetry and pulse oximetry, if suspected. Grade 1 CRS: Give symptomatic treatment; if not improving after 24 hr, give tocilizumab as in Grade 2. If not improving after 3 days, give a single dose of dexamethasone 10 mg IV. Grade 2 CRS (oxygen requirement <40% FiO₂, hypotension responsive to fluids or low dose of one vasopressor, or Grade 2 organ toxicity): 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 of 3 doses in 24 hr and total of 4 doses). If improving, discontinue tocilizumab. Give dexamethasone 10 mg IV once daily and continue until Grade ≤1; then quickly taper as appropriate. If not improving, manage corticosteroids according to Grade 3 or 4. Grade 3 CRS (oxygen requirement >40% FiO2, hypotension requiring high-dose or multiple vasopressors, Grade 3 organ toxicity, or Grade 4 transaminitis): Consider performing an echocardiogram to assess cardiac function and provide intensive care supportive therapy. Give tocilizumab as in Grade 2; if improving, discontinue tocilizumab. Give dexamethasone 10 mg IV 3 times daily and continue until Grade ≤1; then quickly taper as appropriate. If not improving, manage corticosteroids according to Grade 4. Grade 4 CRS (requirements for ventilator support or continuous venovenous hemodialysis, or Grade 4 organ toxicity excluding transaminitis): Consider performing an echocardiogram to assess cardiac function and provide intensive care supportive therapy. Give tocilizumab as in Grade 2; if improving, discontinue tocilizumab. Give methylprednisolone 1000 mg IV once daily for 3 days. If improving, taper corticosteroids; if not improving, consider methylprednisolone 1000 mg 2–3 times a day or alternate therapy (not limited to anakinra, siltuximab, ruxolitinib, cyclophosphamide, IV immune globulin, and antithymocyte globulin).
• 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 for ≥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. Corticosteroids are not recommended for isolated Grades 2 or 3 headaches. Grade 1 neurologic toxicity <72 hr after infusion: Consider dexamethasone 10 mg IV every 12 –24 hr for 2–3 days. Grade 1 neurologic toxicity >72 hr after infusion: Observe patient. Grade 2 neurologic toxicity: Give dexamethasone 10 mg IV every 12 hr for 2–3 days. If no improvement after 24 hr or worsening of neurologic toxicity, ↑ dose and/or frequency of dexamethasone up to a max of 20 mg IV every 6 hr. Grade 3 neurologic toxicity: Give dexamethasone 10–20 mg IV every 6–12 hr. If no improvement after 24 hr or worsening of neurologic toxicity, give methylprednisolone 2 mg/kg loading dose, followed by 0.5 mg/kg 4 times a day; taper within 7 days. Grade 4 neurologic toxicity: Give dexamethasone 20 mg IV every 6 hr. If no improvement after 24 hr or worsening of neurologic toxicity, give high-dose methylprednisolone 1–2 g, repeated every 24 hr if needed; taper as clinically indicated. If cerebral edema suspected: Consider hyperventilation and hyperosmolar therapy. Give high-dose methylprednisolone (1–2 g, repeated every 24 hr if needed; taper as clinically indicated) and cyclophosphamide (1.5 g/m²).
• Monitor for signs/symptoms of HLH/MAS (hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, cytopenia), including fatal and life-threatening reactions.
• Monitor for signs/symptoms of secondary malignancies, including T-cell malignancies such as fatigue, unexplained weight loss, persistent pain, sore throat, lymphadenopathy, and 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). If hypersensitivity reaction or angioedema occurs, discontinue immediately and provide supportive care.

Lab Test Considerations:

• Verify negative pregnancy status in women of reproductive potential.
• Monitor CBC with differential at baseline after infusions. May cause prolonged neutropenia, anemia, and thrombocytopenia. Manage cytopenias with myeloid growth factors and blood products, as needed.
• 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.