Axicabtagene Ciloleucel Package Insert
Axicabtagene Ciloleucel Package Insert
INDICATIONS
1. Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
2. Adult patients with relapsed or refractory large B-cell lymphoma after first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy.
3. This drug is not indicated for the treatment of primary central nervous system lymphoma.
DOSAGE AND ADMINISTRATION
1. Patient Preparation
Before initiating treatment, confirm the patient’s eligibility for this drug, as it is not indicated for the treatment of primary central nervous system lymphoma.
2. Lymphodepleting Chemotherapy
Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m2 intravenously and fludarabine 30 mg/m2 intravenously on the 3rd, 4th, and 5th days before infusion of this drug.
3. Premedication
Administer acetaminophen 650 mg orally and diphenhydramine 12.5 mg intravenously or orally approximately 1 hour before infusion of this drug.
After assessing the potential risks and benefits, consider administering corticosteroids before infusion.
4. Administration
(1) Inspect the product bag for any damage or defects prior to preparation. Do not use if the packaging is compromised.
(2) Confirm the infusion time, and thaw the product bag in advance. Thaw the product bag either in an overwrap using a water bath or by allowing it to thaw at room temperature until there is no visible ice in the infusion bag. Gently mix the contents of the bag to disperse the cell clumps. If visible cell clumps remain, continue to gently mix the contents of the bag. Do not wash, spin down, and/or re-suspend the product in new media before infusion. Once thawed, the product may be stored at room temperature (20°C to 25°C) for up to 3 hours.
(3) Verify the patient’s identity and infusion details, and proceed with infusion immediately after the patient is ready.
5. Target Dose
This product is a cell suspension for intravenous infusion. The dose is based on the number of CAR-positive viable T cells and is weight-based, with a target dose of 2.0 × 106 CAR-positive viable T cells/kg body weight, with a maximum of 2.0 × 108 CAR-positive viable T cells.
6. Administration Precautions
(1) For autologous use only. Ensure that tocilizumab and emergency equipment are available before infusion and during the recovery period.
(2) Do not use a leukodepleting filter. It is recommended to administer the product via a central venous line.
(3) Before infusion, carefully verify the patient’s identity and match it with the information on the product bag. The thawed product may be stored at room temperature for up to 3 hours.
(4) Flush the infusion line with normal saline before infusion. Infuse the entire contents of the product bag over 30 minutes using a gravity or peristaltic pump. After the entire content has been infused, continue the same infusion rate with normal saline to flush the infusion line, ensuring the bag is empty.
(5) This product is an autologous T-cell product. Follow applicable medical waste disposal procedures to avoid potential transmission of infectious diseases.
(6) This product should be administered at a qualified medical facility, and close patient monitoring for signs and symptoms of cytokine release syndrome and neurological toxicities is recommended after infusion.
(7) Advise patients to remain within proximity of the medical facility for at least 4 weeks after infusion to allow for prompt treatment of potential adverse reactions.
7. Dose Modifications
(1) Cytokine Release Syndrome (CRS)
i. Identify and treat the cause of fever, hypoxia, and hypotension. If CRS is suspected, manage according to the recommendations in Table 1.
ii. For patients experiencing Grade 2 or higher CRS (e.g., hypotension requiring intravenous fluids or supplemental oxygen), monitor with continuous cardiac telemetry and pulse oximetry.
iii. For severe CRS, consider performing an echocardiogram to evaluate cardiac function.
iv. For life-threatening CRS, consider intensive care supportive therapy.
(2) Neurological Toxicities
i. Monitor patients for signs and symptoms of neurological toxicities and rule out other causes. Manage according to the recommendations in Table 2.
ii. For patients experiencing Grade 2 or higher neurological toxicities, monitor with continuous cardiac telemetry and pulse oximetry.
iii. For severe or life-threatening neurological toxicities, consider intensive care supportive therapy and levetiracetam for seizure prophylaxis.
ADVERSE REACTIONS
1. In addition to laboratory abnormalities, the most common adverse reactions (≥30%) in non-Hodgkin lymphoma patients were cytokine release syndrome (CRS), fever, hypotension, encephalopathy, fatigue, tachycardia, headache, nausea, febrile neutropenia, diarrhea, musculoskeletal pain, infections of unspecified pathogen, chills, and decreased appetite.
2. The most common Grade 3 or 4 laboratory abnormalities (≥30%) were leukopenia, lymphopenia, neutropenia, anemia, thrombocytopenia, and hypophosphatemia.
CONTRAINDICATIONS
Not clearly defined.
STORAGE
Store in vapor phase of liquid nitrogen at or below -150°C. Thaw before use, and the thawed product may be stored at 20°C to 25°C for up to 3 hours.
POPULATION
Adults. Use in children, pregnant women, and the elderly should be under the guidance of a physician.
DRUG INTERACTIONS
Not clearly defined.
SHELF LIFE
12 months
DOSAGE FORM
Injection
MANUFACTURER
Gilead Sciences, Inc. (USA)
COMPOSITION
This product is an autologous immunocell injection, with the primary active ingredient being anti-CD19 chimeric antigen receptor (CAR)-positive viable T cells (anti-CD19 CAR-T cells).
DESCRIPTION
This product is a cell suspension cryopreserved in a product bag. It requires thawing before infusion, and the thawed product is a white to red cell suspension.
PRECAUTIONS
1. Hypersensitivity Reactions
Monitor for signs and symptoms of hypersensitivity reactions during infusion.
2. Serious Infections
Monitor patients for signs and symptoms of infection and treat appropriately.
3. Prolonged Cytopenias
Patients may exhibit Grade 3 or higher cytopenias lasting several weeks following infusion. Monitor complete blood counts.
4. Hypogammaglobulinemia
Monitor immunoglobulin levels and consider immunoglobulin replacement therapy.
5. Secondary Malignancies
Patients treated with this drug may develop secondary malignancies.
6. Effects on Ability to Drive and Use Machines
Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks after receiving this treatment.
(Reference: FDA Prescribing Information, November 2022)
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