Ciltacabtagene Autoleucel Dosage

Medically reviewed by Drugs.com. Last updated on Nov 4, 2024.

Usual Adult Dose for Multiple Myeloma

0.5 to 1 x 10(6) chimeric antigen receptor (CAR)-positive viable T cells/kg IV once
Maximum dose: 1 x 10(8) CAR-positive viable T cells/single infusion

Comments:

• This drug is provided as a single dose for IV infusion of CAR-positive viable T cells in 1 infusion bag.
• Before starting the lymphodepleting chemotherapy regimen, confirm the availability of this drug.
• This drug should be administered 2 to 4 days after the completion of the lymphodepleting chemotherapy regimen.
• Infusion of this drug should be delayed if a patient has any of the following conditions:
• Clinically significant active infection or inflammatory disorders.
• Grade 3 or higher nonhematologic toxicities of cyclophosphamide and fludarabine conditioning (except for grade 3 nausea, vomiting, diarrhea, or constipation); infusion of this drug should be delayed until these events improve to grade 1 or lower.

Use: For the treatment of patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

MANAGEMENT OF SEVERE ADVERSE REACTIONS AFTER INFUSION OF THIS DRUG:
CYTOKINE RELEASE SYNDROME (CRS):

• Identify CRS based on clinical presentation; evaluate for and treat other causes of fever, hypoxia, and hypotension.
• Consider laboratory testing to monitor for disseminated intravascular coagulation, hematology parameters, in addition to pulmonary, cardiac, renal, and liver function.
• If CRS is suspected, manage according to the recommendations provided below.
• Closely monitor patients with CRS for cardiac and other organ function until symptoms resolve; consider antiseizure prophylaxis with levetiracetam in those with CRS.
• Monitor patients with grade 2 or higher CRS (e.g., hypotension not responsive to fluids, hypoxia requiring supplemental oxygenation) with continuous telemetry and pulse oximetry.
• For severe or life-threatening CRS, consider intensive care unit level monitoring and supportive therapy.
• For CRS refractory to first line interventions (such as tocilizumab or tocilizumab and corticosteroids), consider alternate treatment options (i.e., higher corticosteroid dose, alternative anticytokine agents).
• Refractory CRS is characterized by fevers, end-organ toxicity (e.g., hypoxia, hypotension) not improving within 12 hours of first line interventions, or development of hemophagocytic lymphohistiocytosis/macrophage activation syndrome.

Management with tocilizumab/corticosteroids:

• The tocilizumab dose is 8 mg/kg (up to 800 mg) IV over 1 hour.
• Consult the manufacturer product information of tocilizumab for details.
• Continue corticosteroids until the event is grade 1 or lower; taper steroids if total corticosteroid exposure exceeds 3 days.

CRS Grading and Management Guidance:
Grade 1 CRS (temperature at least 38C [100.4F] due to CRS):

• In patients with early onset of fever (if onset less than 72 hours after infusion): Consider a dose of tocilizumab.

Grade 2 CRS (symptoms require and respond to moderate intervention; temperature at least 38C [due to CRS] with: hypotension not requiring vasopressors, and/or hypoxia requiring oxygen via cannula [low-flow nasal cannula is up to 6 L/min; high-flow nasal cannula is greater than 6 L/min]/blow-by, or grade 2 organ toxicity):

• Administer tocilizumab; repeat every 8 hours as needed if not responsive to IV fluids (up to 1 L) or increasing supplemental oxygen.
• Consider dexamethasone (10 mg IV every 12 to 24 hours).
• If no improvement within 24 hours or rapid progression: Repeat tocilizumab; 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 anticytokine agents (monoclonal antibodies targeting cytokines).
• Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total.

Grade 3 CRS (symptoms require and respond to aggressive intervention; temperature at least 38C [due to CRS] with: hypotension requiring 1 vasopressor with or without vasopressin, and/or hypoxia requiring oxygen via high-flow nasal cannula [greater than 6 L/min]/facemask/non-rebreather mask/Venturi mask, or grade 3 organ toxicity/grade 4 transaminitis):

• Administer tocilizumab; repeat every 8 hours as needed if not responsive to IV fluids (up to 1 L) or increasing supplemental oxygen.
• Consider dexamethasone (10 mg IV every 12 hours).
• If no improvement within 24 hours or rapid progression: Repeat tocilizumab; 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 anticytokine agents (monoclonal antibodies targeting cytokines).
• Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total.

Grade 4 CRS (life-threatening symptoms; requirements for ventilator support, continuous venovenous hemodialysis; temperature at least 38C [due to CRS] with: hypotension requiring multiple vasopressors [excluding vasopressin], and/or hypoxia requiring positive pressure [e.g., continuous positive airway pressure, bilevel positive airway pressure, intubation, mechanical ventilation], or grade 4 organ toxicity [excluding transaminitis]):

• Administer tocilizumab; repeat every 8 hours as needed if not responsive to IV fluids (up to 1 L) or increasing supplemental oxygen.
• Administer dexamethasone (20 mg IV every 6 hours).
• After 2 doses of tocilizumab, consider alternative anticytokine agents (monoclonal antibodies targeting cytokines).
• Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total.
• If no improvement within 24 hours: Consider methylprednisolone (1 to 2 g IV, repeat every 24 hours if needed; taper as clinically indicated) or other immunosuppressants (e.g., other anti-T cell therapies).

NEUROLOGIC TOXICITIES:

• Monitor patients for signs/symptoms of neurologic toxicities (immune effector cell-associated neurotoxicity syndrome [ICANS] and other neurologic toxicities); rule out other causes of neurologic signs/symptoms.
• Provide intensive care and supportive therapy for severe or life-threatening neurologic toxicities; if ICANS is suspected, manage according to the recommendations provided below.

ICANS Grading and Management Guidance:
Grade 1 ICANS (immune effector cell-associated encephalopathy [ICE] score 7 to 9 or depressed level of consciousness [awakens spontaneously]):

• Consider dexamethasone (10 mg IV every 12 to 24 hours) or equivalent for 2 to 3 days.
• Consider nonsedating, antiseizure drugs (e.g., levetiracetam) for seizure prophylaxis.

Grade 2 ICANS (ICE score 3 to 6 or depressed level of consciousness [awakens to voice]):

• Administer dexamethasone (10 mg IV every 12 hours) or equivalent for 2 to 3 days, or longer for persistent symptoms.
• Consider steroid taper if total corticosteroid exposure exceeds 3 days.
• If no improvement after 24 hours or worsening of neurologic toxicity: Increase the dose and/or frequency of dexamethasone (up to 20 mg IV every 6 hours).
• Consider nonsedating, antiseizure drugs for seizure prophylaxis.

Grade 3 ICANS (ICE score 0 to 2 [if ICE score is 0, but patient is arousable (e.g., awake with global aphasia) and able to perform assessment], or depressed level of consciousness [awakens only to tactile stimulus], or seizures [either any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures on electroencephalogram that resolve with intervention], or raised intracranial pressure [ICP] [focal/local edema on neuroimaging]):

• Administer dexamethasone (10 to 20 mg IV every 6 hours) or equivalent.
• If no improvement after 24 hours or worsening of neurologic toxicity: Escalate dexamethasone dose (to at least 20 mg IV every 6 hours) or equivalent OR escalate to high-dose methylprednisolone (1 to 2 g/day, repeat every 24 hours if needed; taper as clinically indicated).
• Consider nonsedating, antiseizure drugs for seizure prophylaxis.
• If cerebral edema is suspected: Consider hyperventilation and hyperosmolar therapy; administer high-dose methylprednisolone (1 to 2 g, repeat every 24 hours if needed; taper as clinically indicated).

Grade 4 ICANS (ICE score 0 [patient is unarousable and unable to perform ICE assessment] or depressed level of consciousness [either patient is unarousable or requires vigorous/repetitive tactile stimuli to arouse, or stupor/coma], or seizures [either life-threatening prolonged seizure (greater than 5 minutes), or repetitive clinical or electrical seizures without return to baseline in between], or motor findings [deep focal motor weakness such as hemiparesis or paraparesis], or raised ICP/cerebral edema, with signs/symptoms [e.g., diffuse cerebral edema on neuroimaging, decerebrate/decorticate posturing, cranial nerve VI palsy, papilledema, Cushing's triad]):

• Administer dexamethasone (20 mg IV every 6 hours) or equivalent.
• If no improvement after 24 hours or worsening of neurologic toxicity: Escalate to high-dose methylprednisolone (1 to 2 g/day, repeated every 24 hours if needed; taper as clinically indicated).
• Consider nonsedating, antiseizure drugs for seizure prophylaxis.
• If raised ICP/cerebral edema is suspected: Consider hyperventilation and hyperosmolar therapy; administer high-dose methylprednisolone (1 to 2 g/day, repeat every 24 hours if needed; taper as clinically indicated), and consider neurology and/or neurosurgery consultation.

CRS AND NEUROLOGIC TOXICITIES:

• If concurrent neurologic toxicity is suspected during CRS or concurrent CRS is suspected during the neurologic toxicity event, administer:
• Corticosteroids according to the more aggressive intervention based on CRS and neurologic toxicity grades
• Tocilizumab according to CRS grade
• Antiseizure therapy according to neurologic toxicity

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for ciltacabtagene autoleucel. It includes elements to assure safe use and an implementation system. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:

• CYTOKINE RELEASE SYNDROME (CRS): CRS (including fatal or life-threatening reactions) has occurred after treatment with this drug. This drug should not be administered to patients with active infection or inflammatory disorders. Severe or life-threatening CRS should be treated with tocilizumab or tocilizumab and corticosteroids.
• NEUROLOGIC TOXICITIES: ICANS (which may be fatal or life-threatening) has occurred after treatment with this drug, including before CRS onset, concurrently with CRS, after resolution of CRS, or without CRS. Patients should be monitored for neurologic events after treatment with this drug; supportive care and/or corticosteroids should be provided as needed. Parkinsonism and Guillain-Barre syndrome and their associated complications resulting in fatal or life-threatening reactions have occurred after treatment with this drug.
• HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS/MACROPHAGE ACTIVATION SYNDROME (HLH/MAS): HLH/MAS (including fatal or life-threatening reactions) has occurred after treatment with this drug; HLH/MAS can occur with CRS or neurologic toxicities.
• PROLONGED AND RECURRENT CYTOPENIA: Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery have occurred after treatment with this drug.
• SECONDARY HEMATOLOGICAL MALIGNANCIES: Secondary hematological malignancies (including myelodysplastic syndrome and acute myeloid leukemia) have occurred after treatment with this drug. T-cell malignancies have occurred after treatment of hematologic malignancies with B-cell maturation antigen-directed and CD19-directed genetically modified autologous T-cell immunotherapies (including this drug).
• CARVYKTI REMS: This drug is available only through a restricted program under a REMS.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer this drug at a REMS-certified health care facility.
• For autologous use only
• The patient's identity must match the patient identifiers on the drug cassette and infusion bag.
• Do not infuse this drug if the information on the patient-specific labels does not match the intended patient.
• For IV use only
• Do NOT use a leukocyte-depleting filter.
• Ensure that at least 2 doses of tocilizumab and emergency equipment are available before infusion and during recovery.
• Central venous access may be used for the infusion and is encouraged in patients with poor peripheral access.
• After the patient's identity has been confirmed with the patient identifiers on the infusion bag:
• Prime the tubing of the infusion set with normal saline before infusion.
• Once thawed, administer the entire contents of the bag by IV infusion within 2.5 hours using infusion sets fitted with an in-line filter.
• Gently mix the contents of the bag during infusion to disperse cell clumps.
• After the entire content of the 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 all product is delivered.
• Monitor patients carefully for 2 hours after infusion for signs/symptoms of severe hypersensitivity reaction.
• Monitor patients at least daily for 10 days after infusion of this drug at a certified health care facility for signs/symptoms of CRS and neurologic toxicities; monitor periodically for 4 weeks for signs/symptoms of delayed neurologic toxicity.

Pretreatment:

• Administer the lymphodepleting chemotherapy regimen (cyclophosphamide 300 mg/m2 IV and fludarabine 30 mg/m2 IV daily for 3 days); consult the manufacturer product information of cyclophosphamide and fludarabine for further information (e.g., dose adjustment in renal dysfunction).
• Delay the lymphodepleting regimen 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 a patient with prior allogeneic stem cell transplant.
• Consider repeating lymphodepleting regimen if dosing of this drug is delayed by more than 14 days and the patient has recovered from the toxicity of the first lymphodepleting regimen.

Premedication:

• Administer antipyretic (oral or IV acetaminophen [650 to 1000 mg]) and antihistamine (oral or IV diphenhydramine [25 to 50 mg] or equivalent) to all patients 30 to 60 minutes before infusion of this drug.
• Avoid prophylactic use of systemic corticosteroids because their use may interfere with the activity of this drug.

Storage requirements:

• Store and transport below -120C (-184F), e.g., in a container for cryogenic storage in the vapor phase of liquid nitrogen.
• Store in the original packaging containing the cassette protecting the infusion bag.
• Thaw before infusion; do not refreeze or refrigerate thawed product.

Reconstitution/preparation techniques:

• Do not thaw the product until it is ready to be used; coordinate the timing of drug thaw and infusion.
• Confirm the infusion time in advance and adjust the start time for thaw so this drug is available for infusion when the patient is ready.
• Once thawed, the infusion of this drug must be completed within 2.5 hours at room/ambient temperature (20C to 25C [68F to 77F]).
• The manufacturer product information should be consulted for further information regarding preparation of this drug for infusion.

General:

• The manufacturer product information should be consulted regarding receipt of this drug.
• This drug contains human blood cells genetically modified with replication-incompetent, self-activating, lentiviral vector; universal precautions and local biosafety guidelines for handling and disposal of this drug should be followed to avoid potential transmission of infectious diseases.

Monitoring:

• Hematologic: Blood counts (before and after infusion)
• Hypersensitivity: For signs/symptoms of severe hypersensitivity reaction (for 2 hours after infusion)
• Immunologic: For signs/symptoms of CRS (after infusion: at least daily for 10 days at the facility, then for at least 4 weeks); immunoglobulin levels (after therapy)
• Infections/Infestations: For signs/symptoms of infection (before and after infusion)
• Nervous System: For signs/symptoms of neurologic toxicities, including ICANS (after infusion: at least daily for 10 days at the facility, then for at least 4 weeks); for signs/symptoms of delayed neurologic toxicity (periodically for 4 weeks); for signs/symptoms of parkinsonism, peripheral neuropathies, and cranial nerve palsies; for Guillain-Barre syndrome
• Oncologic: For secondary malignancies (life-long)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• For at least 4 weeks after infusion, remain within proximity of a certified health care facility.
• Seek immediate medical attention if the following occur:
• Signs/symptoms of CRS (including fever, chills, fatigue, headache, tachycardia, hypotension, hypoxia, dizziness/lightheadedness, organ toxicities).
• Signs/symptoms associated with neurologic events, which may occur days, weeks, or months after the infusion, including ICANS (e.g., aphasia, encephalopathy, depressed level of consciousness, seizures, delirium, dysgraphia), parkinsonism (e.g., tremor, micrographia, bradykinesia, rigidity, shuffling gait, stooped posture, masked facies, apathy, flat affect, lethargy, somnolence), Guillain Barre syndrome (e.g., motor weakness, polyradiculoneuritis), peripheral neuropathy (e.g., peripheral motor and/or sensory nerve dysfunction), or cranial nerve palsies (e.g., facial paralysis, facial numbness).
• Signs/symptoms associated with bone marrow suppression (including neutropenia, thrombocytopenia, anemia, febrile neutropenia) for several weeks or months; these signs/symptoms may recur.
• Signs/symptoms associated with infection.
• Signs/symptoms associated with hypersensitivity reactions (including flushing, chest tightness, tachycardia, difficulty breathing).
• Contact the manufacturer (1-800-526-7736) if you are diagnosed with a secondary malignancy.
• For at least 8 weeks after infusion (and if any new neurological symptoms develop), refrain from driving or engaging in hazardous occupations/activities (e.g., operating heavy/potentially dangerous machinery).
• Do not donate blood, organs, tissues, or cells for transplantation.

Further information

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