Ciltacabtagene autoleucel
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Boxed warning
WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI. Do not administer CARVYKTI 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 (5.2) ] .
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI. Provide supportive care and/or corticosteroids as needed [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.3) ] . Parkinsonism and Guillain-Barré syndrome (GBS) and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI [see Warnings and Precautions (5.3) ] .
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI. HLH/MAS can occur with CRS or neurologic toxicities [see Warnings and Precautions (5.4) ]. Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI [see Warnings and Precautions (5.5) ] . Immune Effector Cell-associated Enterocolitis (IEC-EC), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI [see Warnings and Precautions (5.9) ].
Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients following treatment with CARVYKTI. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI [see Warnings and Precautions (5.10) ] . WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, 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 following treatment with…
Dosing in kidney impairment
See the prescribing information of cyclophosphamide and fludarabine for information on dose adjustment in renal impairment. 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) or active graft versus host disease in patient with prior allogeneic stem cell transplant.
| CRS Grade Based on ASTCT 2019 grading system (Lee et.al, 2019), modified to include organ toxicity. | Tocilizumab Refer to tocilizumab prescribing information for details./ Corticosteroids Continue corticosteroids use until the event is Grade 1 or less; taper steroids if total corticosteroid exposure is greater than 3 days. |
|---|---|
| Grade 1 | |
| Temperature ≥38 °C Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia, as it may be masked by interventions such as antipyretics or anti-cytokine therapy (e.g., tocilizumab or steroids). Absence of fever does not impact CRS management decision. In this case, CRS management is driven by hypotension and/or hypoxia and by the more severe symptom not attributable to any other cause. | In patients with: Early onset of fever (if onset less than 72 hours after infusion)Tocilizumab 8 mg/kg intravenously (IV) over 1 hour (not to exceed 800 mg) may be considered. Corticosteroids: N/A |
| Grade 2 | |
| Symptoms require and respond to moderate intervention. Temperature ≥38 °C with: Hypotension not requiring vasopressors, and/or, Hypoxia requiring oxygen via cannula or blow-by, or, Grade 2 organ toxicity. Organ toxicity grading based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. | 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. Consider dexamethasone 10 mg IV every 12–24 hours. If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dose and frequency 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. After 2 doses of tocilizumab, consider alternative anti-cytokine agents Monoclonal antibodies targeting cytokines may be considered based on institutional practice for unresponsive CRS.. 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 °C with: Hypotension requiring one vasopressor with or without vasopressin, and/or, Hypoxia requiring oxygen via high-flow nasal cannula Low-flow nasal cannula is ≤6 L/min; high-flow nasal cannula is >6 L/min., 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. Consider dexamethasone 10 mg IV every 12 hours. If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dose and frequency 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. After 2 doses of tocilizumab, consider alternative anti-cytokine agents. 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-venous hemodialysis (CVVHD). Temperature ≥38 °C with: Hypotension requiring multiple vasopressors (excluding vasopressin), and/or, Hypoxia requiring positive pressure (e.g., CPAP, BiPAP, intubation, and mechanical ventilation), or, Grade 4 organ toxicity (excluding 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. Administer dexamethasone 20 mg IV every 6 hours. After 2 doses of tocilizumab, consider alternative anti-cytokine agents . Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total. If no improvement within 24 hours, consider methylprednisolone (1–2 g IV, repeat every 24 hours if needed; taper as clinically indicated) or other immunosuppressants (e.g. other anti-T cell therapies). |
Preparation and administration
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Dose CARVYKTI is provided as a single dose for infusion containing a suspension of chimeric antigen receptor (CAR)-positive viable T cells in one infusion bag. The recommended dose range is 0.5–1.0×10 6 CAR-positive viable T cells per kg of body weight, with a maximum dose of 1×10 8 CAR-positive viable T cells per single infusion.
Administration CARVYKTI is for autologous use only. For intravenous use only. The patient's identity must match the patient identifiers on the CARVYKTI cassette and infusion bag. Do not infuse CARVYKTI if the information on the patient-specific labels does not match the intended patient. Preparing the Patient for CARVYKTI Infusion Confirm availability of CARVYKTI prior to starting the lymphodepleting chemotherapy regimen.
Pretreatment Administer the lymphodepleting chemotherapy regimen: cyclophosphamide 300 mg/m 2 intravenously (IV) and fludarabine 30 mg/m 2 IV daily for 3 days. See the prescribing information of cyclophosphamide and fludarabine for information on dose adjustment in renal impairment. 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) or active graft versus host disease in patient with prior allogeneic stem cell transplant.
Consider repeating lymphodepleting regimen if CARVYKTI dosing is delayed by more than 14 days and patient has recovered from toxicity of the first lymphodepleting regimen. Administer CARVYKTI infusion 2 to 4 days after the completion of the lymphodepleting chemotherapy regimen. CARVYKTI infusion should be delayed if a patient has any of the following conditions: Clinically significant active infection or inflammatory disorders.
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. Premedication Administer the following pre-infusion medications to all patients 30 – 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 prophylactic use of systemic corticosteroids because their use may interfere with the activity of CARVYKTI. Receipt of CARVYKTI All sites approved for infusion will support required storage conditions for vapor phase of liquid nitrogen.
CARVYKTI is shipped directly to the cell laboratory or clinical pharmacy associated with the infusion center in the vapor phase of a liquid nitrogen shipper. Confirm the patient's identity with the patient identifiers on the shipper. If the patient is not expected to be ready for same-day administration, before the shipper expires, transfer CARVYKTI to onsite vapor phase of liquid nitrogen storage.
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. Once thawed, the CARVYKTI infusion must be completed within 2.5 hours at room/ambient temperature (20 °C to 25 °C).
Prior to thawing the product, confirm that tocilizumab and emergency equipment are available prior to the infusion and during the recovery period. 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 infusion bag from the cassette if the information on the patient-specific label does not match the intended patient.
Contact Janssen Biotech, Inc. at 1-800-526-7736 if there are any discrepancies between the labels and the patient identifiers. Once patient identification is confirmed, remove the CARVYKTI product bag from the cassette and check that the patient information on the cassette label matches the patient information on the bag label.
Inspect the product bag for any breaches of container integrity, such as breaks or cracks before and after thawing. Do not administer if the bag is compromised, and contact Janssen Biotech, Inc. at 1-800-526-7736. Place the infusion bag inside a sealable plastic bag (preferably sterile) prior to thawing. Thaw CARVYKTI at 37 °C±2 °C using either a water bath or dry thaw method until there is no visible ice in the infusion bag.
Total time from start of thaw until completion of thawing should be no more than 15 minutes. Remove the infusion bag from the sealable plastic bag and wipe dry. 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 pre-filter into a different container, wash, spin down, or resuspend CARVYKTI in new media prior to infusion. Do not re-freeze or refrigerate thawed product. Administration For autologous infusion only. Do NOT use a leukocyte-depleting filter. Confirm that a minimum of two doses of tocilizumab and emergency equipment are available prior to infusion and during the recovery period.
Central venous access may be utilized for the infusion of CARVYKTI and is encouraged in patients with poor peripheral access. 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. Prime the tubing of the infusion set with normal saline prior to infusion.
Once thawed, administer the entire contents of the CARVYKTI bag by intravenous infusion within 2.5 hours using infusion sets fitted with an in-line filter. Gently mix the contents of the bag during CARVYKTI infusion to disperse cell clumps. After the entire content of the product bag is infused, flush the administration line, inclusive of the in-line filter, with normal saline with a volume equal or greater to the total hold up volume of the primary administration set used inclusive of the drip tube, to ensure that all product is delivered.
CARVYKTI contains human blood cells that are genetically modified with replication-incompetent, self-inactivating, lentiviral vector. Follow universal precautions and local biosafety guidelines for handling and disposal of CARVYKTI to avoid potential transmission of infectious diseases. Monitoring After Infusion Monitor patients at least daily for 7 days following CARVYKTI infusion for signs and symptoms of cytokine release syndrome (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.
| CRS Grade Based on ASTCT 2019 grading system (Lee et.al, 2019), modified to include organ toxicity. | Tocilizumab Refer to tocilizumab prescribing information for details./ Corticosteroids Continue corticosteroids use until the event is Grade 1 or less; taper steroids if total corticosteroid exposure is greater than 3 days. |
|---|---|
| Grade 1 | |
| Temperature ≥38 °C Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia, as it may be masked by interventions such as antipyretics or anti-cytokine therapy (e.g., tocilizumab or steroids). Absence of fever does not impact CRS management decision. In this case, CRS management is driven by hypotension and/or hypoxia and by the more severe symptom not attributable to any other cause. | In patients with: Early onset of fever (if onset less than 72 hours after infusion)Tocilizumab 8 mg/kg intravenously (IV) over 1 hour (not to exceed 800 mg) may be considered. Corticosteroids: N/A |
| Grade 2 | |
| Symptoms require and respond to moderate intervention. Temperature ≥38 °C with: Hypotension not requiring vasopressors, and/or, Hypoxia requiring oxygen via cannula or blow-by, or, Grade 2 organ toxicity. Organ toxicity grading based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. | 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. Consider dexamethasone 10 mg IV every 12–24 hours. If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dose and frequency 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. After 2 doses of tocilizumab, consider alternative anti-cytokine agents Monoclonal antibodies targeting cytokines may be considered based on institutional practice for unresponsive CRS.. 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 °C with: Hypotension requiring one vasopressor with or without vasopressin, and/or, Hypoxia requiring oxygen via high-flow nasal cannula Low-flow nasal cannula is ≤6 L/min; high-flow nasal cannula is >6 L/min., 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. Consider dexamethasone 10 mg IV every 12 hours. If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dose and frequency 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. After 2 doses of tocilizumab, consider alternative anti-cytokine agents. 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-venous hemodialysis (CVVHD). Temperature ≥38 °C with: Hypotension requiring multiple vasopressors (excluding vasopressin), and/or, Hypoxia requiring positive pressure (e.g., CPAP, BiPAP, intubation, and mechanical ventilation), or, Grade 4 organ toxicity (excluding 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. Administer dexamethasone 20 mg IV every 6 hours. After 2 doses of tocilizumab, consider alternative anti-cytokine agents . Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total. If no improvement within 24 hours, consider methylprednisolone (1–2 g IV, repeat every 24 hours if needed; taper as clinically indicated) or other immunosuppressants (e.g. other anti-T cell therapies). |
Drug interactions
Check ciltacabtagene autoleucel against a medication listLabel text (1 paragraph)
7 DRUG INTERACTIONS HIV and the lentivirus used to make CARVYKTI have limited, short spans of identical genetic material (RNA). Therefore, some commercial HIV nucleic acid tests (NATs) may yield false-positive results in patients who have received CARVYKTI.
Contraindications
None. None ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary There are no available data on the use of CARVYKTI in pregnant women. No reproductive and developmental toxicity studies in animals have been conducted with CARVYKTI to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known whether CARVYKTI has the potential to be transferred to the fetus and cause fetal toxicity. Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia and hypogammaglobulinemia. Therefore, CARVYKTI is not recommended for women who are pregnant, or for women of childbearing potential not using contraception.
Pregnant women should be advised that there may be risks to the fetus. Pregnancy after CARVYKTI therapy 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)
Therapeutic equivalence (Orange Book)
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Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.