Axicabtagene ciloleucel
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Boxed warning
WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving YESCARTA. Do not administer YESCARTA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.1) ] . Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving YESCARTA, including concurrently with CRS or after CRS resolution.
Monitor for neurologic toxicities after treatment with YESCARTA. Provide supportive care and/or corticosteroids as needed [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.2) ] . T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA [see Warnings and Precautions (5.7) ] . WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES See full prescribing information for complete boxed warning .
Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving YESCARTA. Do not administer YESCARTA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids ( 2.2 , 2.3 , 5.1 ). Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving YESCARTA, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with YESCARTA. Provide supportive care and/or corticosteroids, as needed ( 2.2 , 2.3 , 5.2 ).
T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA ( 5.7 ).
CD19-directed Chimeric Antigen Receptor, Genetically-modified Autologous T Cells
Dosing in kidney impairment
Key manifestations of CRS (≥ 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) [see Adverse Reactions ].
| CRS Grade Lee et al. 2014. | Tocilizumab | Corticosteroids |
|---|---|---|
| Grade 1 Symptoms require symptomatic treatment only (e.g., fever, nausea, fatigue, headache, myalgia, malaise). | If symptoms (e.g., fever) not improving after 24 hours, consider managing as Grade 2. | If not improving after 3 days, administer one dose of dexamethasone 10 mg intravenously. |
| Grade 2 Symptoms require and respond to moderate intervention. Oxygen requirement less than 40% FiO2 or hypotension responsive to fluids or low-dose of one vasopressor or Grade 2 organ toxicity.Refer to Table 2 for management of neurologic toxicity. | Administer tocilizumabRefer to tocilizumab Prescribing Information for details. 8 mg/kg intravenously over 1 hour (not to exceed 800 mg). If no clinical improvement in the signs and symptoms of CRS after the first dose, repeat tocilizumab every 8 hours as needed. Limit to a maximum of 3 doses in a 24-hour period; maximum total of 4 doses. If improving, discontinue tocilizumab. | Administer dexamethasone 10 mg intravenously once daily. If improving, manage as Grade 1 above and continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as appropriate grade below. |
| Grade 3 Symptoms require and respond to aggressive intervention. Oxygen requirement greater than or equal to 40% FiO2 or hypotension requiring high-dose or multiple vasopressors or Grade 3 organ toxicity or Grade 4 transaminitis. | Per Grade 2. If improving, manage as appropriate grade above. | Dexamethasone 10 mg intravenously three times a day. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then quickly taper as clinically appropriate. If not improving, manage as Grade 4. |
| Grade 4 Life-threatening symptoms. Requirements for ventilator support, continuous veno-venous hemodialysis (CVVHD) or Grade 4 organ toxicity (excluding transaminitis). | Per Grade 2. If improving, manage as appropriate grade above. | Administer methylprednisolone 1000 mg intravenously once per day for 3 days. If improving, manage as appropriate grade above and continue corticosteroids until the severity is Grade 1 or less, then taper as clinically appropriate. If not improving, consider methylprednisolone 1000 mg 2-3 times a day or alternate therapy.Alternate therapy includes (but is not limited to): anakinra, siltuximab, ruxolitinib, cyclophosphamide, IVIG and ATG. |
Preparation and administration
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Dose For autologous use only. For intravenous use only. Each single infusion bag of YESCARTA contains a suspension of chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL. The target dose is 2 × 10 6 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 10 8 CAR-positive viable T cells.
Administration YESCARTA is for autologous use only. The patient's identity must match the patient identifiers on the YESCARTA cassette and infusion bag. Do not infuse YESCARTA if the information on the patient-specific label does not match the intended patient. Preparing Patient for YESCARTA Infusion Confirm availability of YESCARTA prior to starting the lymphodepleting regimen.
Pre-treatment Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m 2 intravenously and fludarabine 30 mg/m 2 intravenously on the fifth, fourth, and third day before infusion of YESCARTA. Premedication Administer acetaminophen 650 mg PO and diphenhydramine 12.5 mg intravenously or PO approximately 1 hour before YESCARTA infusion.
Consider the use of prophylactic corticosteroid in patients after weighing the potential benefits and risks [see Warnings and Precautions (5.1 and 5.2) ] . Preparation of YESCARTA for Infusion Coordinate the timing of YESCARTA thaw and infusion. Confirm the infusion time in advance, and adjust the start time of YESCARTA thaw such that it will be available for infusion when the patient is ready.
Confirm patient identity: Prior to YESCARTA preparation, match the patient's identity with the patient identifiers on the YESCARTA cassette. Do not remove the YESCARTA product bag from the cassette if the information on the patient-specific label does not match the intended patient. Once patient identification is confirmed, remove the YESCARTA product bag from the cassette and check that the patient information on the cassette label matches the bag label.
Inspect the product bag for any breaches of container integrity such as breaks or cracks before thawing. If the bag is compromised, follow the local guidelines (or call Kite at 1-844-454-KITE). Place the infusion bag inside a second sterile bag per local guidelines. Thaw YESCARTA at approximately 37°C using either a water bath or dry thaw method until there is no visible ice in the infusion bag.
Gently mix the contents of the bag to disperse clumps of cellular material. If visible cell clumps remain continue to gently mix the contents of the bag. Small clumps of cellular material should disperse with gentle manual mixing. Do not wash, spin down, and/or re-suspend YESCARTA in new medium prior to infusion. Once thawed, YESCARTA may be stored at room temperature (20°C to 25°C) for up to 3 hours.
Administration For autologous use only. Confirm that tocilizumab and emergency equipment are available prior to infusion and during the recovery period. Do NOT use a leukodepleting filter. Central venous access is recommended for the infusion of YESCARTA. Confirm the patient's identity matches the patient identifiers on the YESCARTA product bag.
Prime the tubing with normal saline prior to infusion. Infuse the entire contents of the YESCARTA bag within 30 minutes by either gravity or a peristaltic pump. YESCARTA is stable at room temperature for up to 3 hours after thaw. Gently agitate the product bag during YESCARTA infusion to prevent cell clumping. After the entire content of the product bag is infused, rinse the tubing with normal saline at the same infusion rate to ensure all product is delivered.
YESCARTA contains human blood cells that are genetically modified with replication incompetent retroviral vector. Follow universal precautions and local biosafety guidelines for handling and disposal to avoid potential transmission of infectious diseases. Monitoring Monitor patients at least daily for 7 days following infusion for signs and symptoms of CRS and neurologic toxicities.
Instruct patients to remain within proximity of a healthcare facility for at least 2 weeks following infusion. Advise patients to avoid driving for at least 2 weeks following infusion.
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary There are no available data with YESCARTA use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with YESCARTA to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if YESCARTA has the potential to be transferred to the fetus. Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia. Therefore, YESCARTA is not recommended for women who are pregnant, and pregnancy after YESCARTA infusion should be discussed with the treating physician. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% – 4% and 15% – 20%, respectively.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
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