BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR YESCARTA™
( axicabtagene ciloleucel ) suspension for intravenous infusion
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Table 1 . CRS Grading and Management Guidance ( continued ) |
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SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION |
CRS Grade ( a )
Grade 3
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Tocilizumab
Per Grade 2
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Corticosteroids
Administer methylprednisolone
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WARNING : CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES
• 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
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Symptoms require and respond to aggressive intervention .
Oxygen requirement greater than or equal to 40 % FiO 2 or hypotension requiring high-dose or multiple vasopressors or
Grade 3 organ toxicity or Grade 4 transaminitis .
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1 mg / kg intravenously twice daily or equivalent dexamethasone ( e . g .,
10 mg intravenously every
6 hours ).
Continue corticosteroids use until the event is Grade 1 or less , then taper over 3 days .
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needed [ see Dosage and Administration ( 2.2 , 2.3 ), Warnings and Precautions ( 5.2 )]. |
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• YESCARTA is available only through a restricted program under a Risk Evaluation and Mitigation |
Grade 4 |
Per Grade 2 |
Administer methylprednisolone |
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Strategy ( REMS ) called the YESCARTA REMS [ see Warnings and Precautions ( 5.3 )].
1 INDICATIONS AND USAGE
YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of 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 , primary
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Life-threatening symptoms .
Requirements for ventilator support , continuous veno-venous hemodialysis ( CVVHD ) or
Grade 4 organ toxicity ( excluding transaminitis ).
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1000 mg intravenously per day for 3 days ; if improves , then manage as above . |
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mediastinal large B-cell lymphoma , high grade B-cell lymphoma , and DLBCL arising from follicular lymphoma .
Limitation of Use : YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma .
2 DOSAGE AND ADMINISTRATION
2.2 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
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( a ) Lee et al 2014 , ( b ) Refer to Table 2 for management of neurologic toxicity , ( c ) Refer to tocilizumab Prescribing Information for details
Neurologic Toxicity : Monitor patients for signs and symptoms of neurologic toxicities ( Table 2 ). Rule out other causes of neurologic symptoms . Patients who experience Grade 2 or higher neurologic toxicities should be monitored with continuous cardiac telemetry and pulse oximetry . Provide intensive care supportive therapy for severe or life threatening neurologic toxicities . Consider non-sedating , anti-seizure medicines ( e . g ., levetiracetam ) for seizure prophylaxis for any Grade 2 or higher neurologic toxicities .
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patient-specific label does not match the intended patient [ see Dosage and Administration ( 2.2.3 )].
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 ,
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Table 2 . Neurologic Toxicity Grading and Management Guidance
Grading
Concurrent CRS
Assessment
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No Concurrent CRS |
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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 . Avoid prophylactic use of systemic corticosteroids , as it may interfere with the activity of YESCARTA .
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
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Grade 2 |
Administer tocilizumab per Table 1 for management of Grade 2 CRS .
If no improvement within 24 hours after starting tocilizumab , administer dexamethasone 10 mg intravenously every 6 hours if not already taking other corticosteroids . Continue dexamethasone use until the event is Grade 1 or less , then taper over 3 days .
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Administer dexamethasone 10 mg intravenously every 6 hours .
Continue dexamethasone use until the event is Grade 1 or less , then taper over 3 days .
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information on the cassette label matches the bag label . Inspect the product bag for any breaches of container
Consider non-sedating , anti-seizure medicines ( e . g ., levetiracetam ) for seizure integrity such as breaks or cracks before thawing . If the bag is compromised , follow the local guidelines ( or prophylaxis . 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 Print-only
Grade 3content
Administer tocilizumab per Table 1 for
Administer dexamethasone 10 mg the infusion bag . Gently mix the contents of the bag to disperse clumps of cellular material . If visible cell clumps management of Grade 2 CRS . intravenously every 6 hours . 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 media prior to infusion .
In addition , administer dexamethasone 10 mg
Continue dexamethasone use until
Once thawed , YESCARTA may be stored at room temperature ( 20 ° C to 25 ° C ) for up to 3 hours . intravenously with the first dose of tocilizumab the event is Grade 1 or less , then and repeat dose every taper over 3 days .
Administration : For autologous use only . Ensure that tocilizumab and emergency equipment are available
6 hours . Continue dexamethasone use until the prior to infusion and during the recovery period . Do NOT use a leukodepleting filter . Central venous access is event is Grade 1 or less , then taper over 3 days . recommended for the infusion of YESCARTA . Confirm the patient ’ s identity matches the patient identifiers on
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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 : Administer YESCARTA at a certified healthcare facility . Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS and neurologic toxicities . Instruct patients to remain within proximity of the certified healthcare facility for at least 4 weeks following infusion .
2.3 Management of Severe Adverse Reactions Cytokine Release Syndrome ( CRS ): Identify CRS based on clinical presentation [ see Warnings and
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Grade 4 |
Consider non-sedating , anti-seizure medicines ( e . g ., levetiracetam ) for seizure prophylaxis .
Administer tocilizumab per Table 1 for
Administer methylprednisolone management of Grade 2 CRS .
1000 mg intravenously per day for
Administer methylprednisolone
3 days ; if improves , then manage
1000 mg intravenously per day with first dose of as above . tocilizumab and continue methylprednisolone
1000 mg intravenously per day for 2 more days ; if improves , then manage as above .
Consider non-sedating , anti-seizure medicines ( e . g ., levetiracetam ) for seizure prophylaxis .
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Precautions ( 5.1 )]. Evaluate for and treat other causes of fever , hypoxia , and hypotension . If CRS is suspected , manage according to the recommendations in Table 1 . Patients who experience Grade 2 or higher
CRS ( e . g ., hypotension , not responsive to fluids , or hypoxia requiring supplemental oxygenation ) should be
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4 CONTRAINDICATIONS : None .
5 WARNINGS AND PRECAUTIONS
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monitored with continuous cardiac telemetry and pulse oximetry . For patients experiencing severe CRS , | ||||||
consider performing an echocardiogram to assess cardiac function . For severe or life-threatening CRS , | ||||||
consider intensive care supportive therapy . | ||||||
Table 1 . CRS Grading and Management Guidance | ||||||
CRS Grade ( a ) |
Tocilizumab |
Corticosteroids |
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Grade 1
Symptoms require symptomatic treatment only ( e . g ., fever , nausea , fatigue , headache , myalgia , malaise ).
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N / A |
N / A |