Usual Adult Dose for Multiple Myeloma

Provided as one bag with a single dose for IV infusion:
Recommended dose range: 0.5 to 1.0 × 10(6) CAR-positive viable T cells per kg of body weight
Maximum dose of 1×10(8) CAR-positive viable T cells per single infusion
Treatment duration: The single IV infusion should be administered within 2.5 hours

Comments:

• This drug is for autologous use only. The patient identity must match the identifiers on the drug cassette and infusion bag. Do not use if the information on the patient-specific labels does not match.

Use: For the treatment of adult patients with relapsed or refractory multiple myeloma, after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD 38 monoclonal antibody.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Precautions

US FDA requires a medication guide to assure safe use. For additional information: www.fda.gov/drugs/drug-safety-and-availability/medication-guides

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for CARVYKTI. It includes a medication guide, communication plan, elements to assure safe use, and implementation system. Further information is available at www.carvyktirems.com or 1-844-672-0067 or www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
Cytokine Release Syndrome (CRS):

• CRS, including fatal or life-threatening reactions, have been reported in patients following treatment with this drug.
• Do not administer to patients with active infection or inflammatory disorders.
• Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids (see manufacturers prescribing information for further grading and management instructions).

Neurologic Toxicities:

• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), may be fatal or life-threatening, and has occurred following treatment with this drug, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS.
• Patients should be monitored for neurologic events after treatment.
• Provide supportive care and/or corticosteroids as needed (see manufacturers prescribing information for further management instructions).

• Parkinsonism and Guillain-Barré syndrome and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with this drug.

• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with this drug.
• HLH/MAS can occur with CRS or neurologic toxicities.
• Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment.

• This drug is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI REMS Program.

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:

• See pretreatment and premedication instructions below.
• This drug is for autologous use only. The patient's identity must match the patient identifiers on the drug's cassette and infusion bag. Do not infuse if the information on the patient-specific labels does not match the patient.
• Do NOT use a leukocyte-depleting filter.
• A minimum of two doses of tocilizumab and emergency equipment should be available prior to infusion and during the recovery period.
• Central venous access may be utilized for the infusion especially in patients with poor peripheral access.
• Prime the tubing of the infusion set with normal saline prior to infusion
• Once thawed, administer the entire contents of the bag IV 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.
• Once the entire content of the bag is infused, flush the IV line, including the in-line filter, with normal saline with a volume equal or greater to the total volume of the primary administration set used inclusive of the drip tube, to ensure that all product is delivered.
• This drug 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 to avoid potential transmission of infectious diseases.

Pretreatment

• Administer the lymphodepleting chemotherapy regimen: cyclophosphamide 300 mg/m2 IV and fludarabine 30 mg/m2 IV daily for 3 days.
• See the prescribing information of cyclophosphamide and fludarabine for further information about this regimen.
• Administer infusion with this drug 2 to 4 days after the completion of the lymphodepleting chemotherapy regimen.
• Infusion should be delayed if the patient has:
• Clinically significant active infection or inflammatory disorders
• Grade 3 or greater non-hematologic toxicities of cyclophosphamide and fludarabine conditioning, except for Grade 3 nausea, vomiting, diarrhea, or constipation. Delay infusion until resolution of these events to Grade 1 or less.

Premedication

• Administer pre-infusion medications 30 to 60 minutes prior to this drug:
• Antipyretics (oral or IV acetaminophen 650 to 1000 mg).
• Antihistamine (oral or IV diphenhydramine 25 to 50 mg or equivalent).

Reconstitution/preparation techniques:

• Read the US FDA-approved patient labeling for further receipt, preparation, and administration instructions.

Storage requirements:

• Store and transport below -120 C (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 prior to infusion

General:

• This drug should be administered at a REMS-certified healthcare facility.
• Instruct patients to remain within proximity of a certified healthcare facility for at least 4 weeks following infusion.
• Instruct patients to refrain from driving or hazardous activities for at least 8 weeks following infusion.

Monitoring:

• Monitor patients at least daily for 10 days following infusion for signs and symptoms of cytokine release syndrome (CRS) and neurologic toxicities.
• Patients immunoglobulin levels should be monitored after treatment.
• Monitor periodically for 4 weeks for signs and symptoms of delayed neurologic toxicity.
• Read the US FDA-approved patient labeling for CRS, neurologic toxicities, and other severe adverse reactions management.

Patient advice:

• Read the Patient Information and Instructions for Use.