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CARVYKTI is a brand name for Ciltacabtagene Autoleucel, supplied as a suspension. The medicine, its uses, side effects and dosage are the same regardless of brand.
Verbatim from this product's HC label. Tap a section to expand.
). Appropriate prophylactic and therapeutic treatment for infections should be provided, and complete resolution of any active infections should be ensured prior to CARVYKTI infusion. Infections may also occur concurrently with CRS and may increase the risk of a fatal event.
Ensure that at least two doses of tocilizumab are available prior to infusion of CARVYKTI. Monitor patients for signs and symptoms of CRS daily for 14 days after the CARVYKTI infusion at a qualified healthcare facility and then periodically for an additional two weeks after CARVYKTI infusion.
Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids, as indicated in Table 2 (see 4 DOSAGE AND ADMINISTRATION).
Evaluation for HLH should be considered in patients with severe or unresponsive CRS. For patients with high pre-infusion tumour burden, early onset of fever, or persistent fever after 24 hours, early tocilizumab should be considered.
The use of myeloid growth factors, particularly granulocyte macrophage-colony stimulating factor (GM-CSF), should be avoided during CRS. Consider reducing baseline burden of disease with bridging therapy prior to infusion with CARVYKTI in patients with high tumour burden.
Management of Cytokine Release Syndrome If CRS is suspected, manage according to the recommendations in Table 2. Administer supportive care for CRS (including but not limited to anti-pyretic agents, IV fluid support, vasopressors, supplemental oxygen) as appropriate.
Consider laboratory testing to monitor for disseminated intravascular coagulation, hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function. Other monoclonal antibodies targeting cytokines (for example, anti-IL1 and/or anti-TNFα) or therapy directed at reduction and elimination of CAR-T-cells may be considered for patients who develop high grade CRS and HLH that remains severe or life-threatening following prior administration of tocilizumab and corticosteroids.
If concurrent neurologic toxicity is suspected during CRS, administer: • Corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades in Table 2 and Table 3, • Tocilizumab according to the CRS grade in Table 2, • Anti-seizure medication according to the neurologic toxicity in Table 3.
0 Page 12 of 50 Temperature ≥38°Cc intravenously (IV) over 1 hour (not to exceed 800 mg) may be considered Grade 2 Symptoms require and respond to moderate intervention.
Temperature ≥38°Cc with:
Hypotension not requiring vasopressors, and/or, Hypoxia requiring oxygen via cannulae or blow-by, or, Grade 2 organ toxicity. Administer tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg). Repeat tocilizumab every 8 hours as needed if not responsive to intravenous fluids up to 1 liter or increasing supplemental oxygen.
). T-cell malignancies have occurred, including fatal outcomes, following treatment with genetically modified autologous T-cell immunotherapies and may present as soon as weeks following infusion. T- cell lymphoma, including CAR-positive tumors, have occurred in patients after CARVYKTI infusion (see 7 WARNINGS AND PRECAUTIONS, Gastrointestinal and 8 ADVERSE REACTIONS).
Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact the company for reporting and to obtain instructions on patient samples to collect for testing of secondary malignancy of T-cell origin.
In patients with HIV infection, contact the company to obtain instructions for the testing of all types of secondary malignancy, including those of non-T-cell origin. Driving and Operating Machinery Due to the potential for neurologic events, patients receiving CARVYKTI are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI infusion.
0 Page 10 of 50 neurological symptoms. 5 Post-Market Adverse Reactions). Significant weight loss has been reported, and supportive care, including total parenteral nutrition (TPN), may be warranted. Cases of gastrointestinal perforation, including fatal outcomes, have been reported.
Prompt referral to gastroenterology and infectious disease specialists should be considered. Treatment with corticosteroids or other immunosuppressants have been reported with variable response. In cases of refractory events, consider additional workup to exclude alternative etiologies, including T-cell lymphoma of the gastrointestinal tract (see 7 WARNINGS AND PRECAUTIONS, Carcinogenesis and Mutagenesis and 8 ADVERSE REACTIONS).
Hematologic Prolonged and Recurrent Cytopenias Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and CARVYKTI infusion and should be managed according to local guidelines. In trials of CARVYKTI, nearly all patients had one or more Grade 3 or 4 cytopenic adverse reactions.
4 Geriatrics). 2 Contraindications CARVYKTI is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
3 Serious Warnings and Precautions Box Serious Warnings and Precautions Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving CARVYKTI. Do not administer CARVYKTI to patients with clinically significant active infection.
Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids (see 7 WARNINGS AND PRECAUTIONS). Neurologic toxicities (Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), Parkinsonism, Guillain-Barré Syndrome and other neurologic toxicities), including fatal or life- threatening reactions, occurred in patients receiving CARVYKTI, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS.
Monitor for neurologic toxicities after treatment with CARVYKTI. Provide supportive care and/or corticosteroids as needed (see 7 WARNINGS AND PRECAUTIONS). 0 Page 6 of 50 Hemophagocytic Lymphohistiocytosis (HLH)/ Macrophage activation syndrome (MAS), including fatal or life-threatening reactions, occurred in patients receiving CARVYKTI in association with CRS and/or neurological toxicities (see 7 WARNINGS AND PRECAUTIONS).
CARVYKTI should be administered by experienced healthcare professionals at qualified treatment centres (see 7 WARNINGS AND PRECAUTIONS). 1 Dosing Considerations • For autologous use only; do not infuse CARVYKTI if the information on the patient-specific label does not match the intended patient.
• For intravenous use only; do NOT use a leukodepleting filter. • CARVYKTI infusion should be delayed if a patient has any of the following conditions: clinically significant active infection, Grade ≥3 non-hematologic toxicities of cyclophosphamide and fludarabine conditioning except for Grade 3 nausea, vomiting, diarrhea, or constipation.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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, 10 mg IV every 6 hours). If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dose of dexamethasone (20 mg IV every 6 to 12 hours). d Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total.
Grade 3 Symptoms require and respond to aggressive intervention.
Temperature ≥38°Cc with:
Hypotension requiring one vasopressor with or without vasopressin, and/or, Hypoxia requiring oxygen via high-flow nasal cannulae, facemask, non-rebreather mask, or Venturi mask, or, Grade 3 organ toxicity or Grade 4 transaminitis. Administer tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg).
Repeat tocilizumab every 8 hours as needed if not responsive to intravenous fluids up to 1 liter or increasing supplemental oxygen. , 10 mg IV every 6 hours). If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dose of dexamethasone (20 mg IV every 6 to 12 hours).
If no improvement within 24 hours or continued rapid progression, switch to methylprednisolone 2 mg/kg IV every 12 hours. d Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total. Grade 4 Life-threatening symptoms. Requirements for ventilator support, continuous veno- Administer tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg).
Repeat tocilizumab every 8 hours as needed if not Administer dexamethasone 20 mg IV every 6 hours. 0 Page 13 of 50 venous hemodialysis (CVVHD). , CPAP, BiPAP, intubation, and mechanical ventilation), or, Grade 4 organ toxicity (excluding transaminitis).
responsive to intravenous fluids up to 1 liter or increasing supplemental oxygen. After 2 doses of tocilizumab, consider alternative anti-cytokine agentsd. Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total. g. other anti-T cell therapies).
al, 2019), modified to include organ toxicity. bRefer to tocilizumab prescribing information for details. cAttributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia, as it may be masked by interventions such […]
Most patients had a median time from infusion to first onset of Grade 3 or 4 cytopenia of less than two weeks with the majority of patients recovering to ≤ Grade 2 by Day 30 (see 8 ADVERSE REACTIONS). Monitor blood counts after CARVYKTI infusion.
For thrombocytopenia consider supportive care with transfusions. Prolonged neutropenia has been associated with increased risk of infection. Myeloid growth factors, particularly GM-CSF, have the potential to worsen CRS symptoms and are not recommended during the first 3 weeks after CARVYKTI or until CRS has resolved.
In the event of febrile neutropenia, infections (see 7 WARNINGS AND PRECAUTIONS, Infections) should be evaluated and managed appropriately with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated. Immune Cytokine Release Syndrome Cytokine release syndrome (CRS), including fatal or life-threatening reactions, can occur after CARVYKTI infusion.
In Study MMY2001, nearly all patients experienced CRS after CARVYKTI infusion with majority of these being Grade 1 or Grade 2 (see 8 ADVERSE REACTIONS). The median time from CARVYKTI infusion (Day 1) to onset of CRS was 7 days (range of 1 to 12 days).
Approximately 90% of patients experienced onset of CRS after Day 3 of receiving the CARVYKTI infusion. In almost all cases, duration of CRS ranged from 1 to 14 days (median duration 4 days) with 88% of patients having a CRS duration of ≤ 7 days.
In Study MMY3002, 151/196 (77%) experienced CRS after CARVYKTI infusion with majority of these being Grade 1 or Grade 2 (see 8 ADVERSE REACTIONS). The median time from CARVYKTI infusion (Day 1) to onset of CRS was 8 days (range of 1 to 23 days).
In all cases, duration of CRS ranged from 1 to 17 days (median duration 3 days), with 89% of patients having a CRS duration of ≤ 7 days. 0 Page 11 of 50 Clinical signs and symptoms of CRS may include but are not limited to fever (with or without rigors), chills, hypotension, hypoxia and elevated liver enzymes.
Potentially life-threatening complications of CRS may include cardiac dysfunction, neurologic toxicity, and HLH. Patients who develop HLH may have an increased risk of severe bleeding. Patients should be closely monitored for signs or symptoms of these events, including fever.
Risk factors for severe CRS include high pre-infusion tumour burden, active infection and early onset of fever or persistent fever after 24 hours of symptomatic treatment. Delay the infusion of CARVYKTI if the patient has unresolved serious adverse reactions from preceding lymphodepleting or bridging therapies (including cardiac toxicity and pulmonary toxicity), rapid disease progression and clinically significant active infection (see 4 DOSAGE AND ADMINISTRATION).
Appropriate prophylactic and therapeutic treatment for infections should be provided, and complete resolution of any active infections should be ensured prior to CARVYKTI infusion. Infections may also occur concurrently with CRS and may increase the risk of a fatal event.
Ensure that at least two doses of tocilizumab are available prior to infusion of CARVYKTI. Monitor patients for signs and symptoms of CRS daily for 14 days after the CARVYKTI infusion at a qualified healthcare facility and then periodically for an additional two weeks after CARVYKTI infusion.
Counsel patients to seek immediate medical attention should […]
CARVYKTI infusion should be delayed until resolution of these events to Grade ≤1. 2 Recommended Dose and Dosage Adjustment CARVYKTI is provided as a single-dose for infusion containing a suspension of chimeric antigen receptor (CAR)-positive viable T-cells.
0×106 CAR-positive viable T-cells per kg of body weight, with a maximum dose of 1×108 CAR-positive viable T-cells per single infusion.
Pediatric (<18 years):
Health Canada has not authorized an indication for pediatric use.
Geriatrics (≥65 years of age):
No dose adjustment is required in patients over 65 years of age (see 10 CLINICAL PHARMACOLOGY). 4 Administration • Administer CARVYKTI at a qualified healthcare facility. • Prior to infusion and during the recovery period, ensure that a minimum of 2 doses of tocilizumab and emergency equipment are available for use.
• Confirm the patient’s identity with the patient identifiers on the infusion bag. Do not infuse CARVYKTI if the information on the patient-specific label does not match the intended patient. • Do NOT use a leukodepleting filter. For special precautions for handling and disposal, see 12 SPECIAL HANDLING INSTRUCTIONS.
Preparing Patient for CARVYKTI Infusion Confirm availability of CARVYKTI prior to starting the lymphodepleting regimen. Lymphodepleting regimen Administer a lymphodepleting regimen of cyclophosphamide 300 mg/m2 intravenously daily and fludarabine 30 mg/m2 intravenously daily for 3 days.
0 Page 7 of 50 start of the lymphodepleting regimen. If resolution of toxicities due to the lymphodepleting regimen to Grade 1 or lower takes more than 14 days, resulting in delays to CARVYKTI dosing, the lymphodepleting regimen should be re-administered after a minimum of 21 days following the first dose of the first - lymphodepleting regimen.
For dose modifications, see the corresponding Product Monographs. Lymphodepleting regimen must be delayed if a patient has serious adverse reactions from preceding bridging therapies (including clinically significant active infection, cardiac toxicity, and pulmonary toxicity).
Clinical assessment prior to CARVYKTI infusion CARVYKTI infusion should be delayed if a patient has any of the following conditions: • clinically significant active infection. • clinically significant active inflammatory disorder. • Grade ≥ 3 non-hematologic toxicities of cyclophosphamide and fludarabine conditioning except for Grade 3 nausea, vomiting, diarrhea, or constipation.
CARVYKTI infusion should be delayed until resolution of these events to Grade ≤ 1. • active graft versus host disease. Premedication Administer the following pre-infusion medications to all patients (30 to 60 minutes) prior to CARVYKTI infusion: • Antipyretics (oral or intravenous acetaminophen 650 to 1000 mg).
• Antihistamine (oral or intravenous diphenhydramine 25 to 50 mg or equivalent). Avoid use of prophylactic systemic corticosteroids as it may interfere with the activity of CARVYKTI. Preparation of CARVYKTI for Infusion Do not thaw the product until it is ready to be used.
Coordinate the timing of CARVYKTI thaw and infusion. Confirm the infusion time in advance and adjust the start time for thaw so that CARVYKTI is available for infusion when the patient is ready. 1.
Confirm patient identity:
Prior to CARVYKTI preparation, match the patient’s identity with the patient identifiers on the CARVYKTI cassette. Do not remove the CARVYKTI product bag from the cassette if the information on the patient-specific label does not match the intended patient.
2. Once patient identification is confirmed, remove the CARVYKTI product bag from the cassette. 3. Inspect the product bag for any breaches of […]