Carvykti for relapsed or refractory multiple myeloma in adults

Carvykti is a suspension of genetically modified autologous T cells designed to target B-cell maturation antigen (BCMA), used for intravenous infusion. It is approved to treat adult patients with relapsed or refractory multiple myeloma who have received at least one prior therapy including a proteasome inhibitor and an immunomodulatory agent and are refractory to lenalidomide.

Indication: Carvykti is indicated for adults with relapsed or refractory multiple myeloma who have been treated with at least one prior line of therapy that included a proteasome inhibitor and an immunomodulatory drug and are refractory to lenalidomide.

ciltacabtagene autoleucel, dimethyl sulfoxide

Carvykti works by using the patient's own T cells that have been genetically engineered to express a chimeric antigen receptor (CAR) targeting BCMA on multiple myeloma cells. This modification enables the T cells to recognize and kill malignant plasma cells displaying BCMA.

Dosage and Administration

Carvykti is given as a single intravenous infusion containing a suspension of CAR-positive viable T cells.

• Recommended dose: 0.5 to 1.0 × 106 CAR-positive viable T cells per kg of body weight, up to a maximum of 1 × 108 cells per infusion.
• Before infusion, patients must receive lymphodepleting chemotherapy with cyclophosphamide (300 mg/m2 IV) and fludarabine (30 mg/m2 IV) daily for 3 days.
• Infuse Carvykti 2 to 4 days after completing lymphodepletion.
• Premedicate 30–60 minutes prior to infusion with acetaminophen and an H1-antihistamine; avoid prophylactic systemic corticosteroids as they may reduce Carvykti effectiveness.
• Infuse over no more than 2.5 hours at room temperature (20–25 °C) after thawing the product at 37 °C.
• Verify patient identity carefully to match with product labels; do not use leukodepleting filters.
• Ensure availability of tocilizumab and emergency equipment prior to and after infusion for management of side effects.

Do not administer Carvykti to patients with clinically significant active infection or inflammatory disorders. Infusion should be delayed for Grade ≥3 non-hematologic toxicities from lymphodepleting chemotherapy (excluding certain GI symptoms) until resolved to Grade ≤1.

Boxed Warnings and Serious Precautions

• Cytokine Release Syndrome (CRS): Can be life-threatening or fatal. Do not administer in patients with active infections or inflammatory disorders. Treat severe CRS with tocilizumab ± corticosteroids. Monitor patients daily for at least 7 days post-infusion.
• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Can occur before, during, or after CRS or independently; may be life-threatening. Monitor neurologic status closely and provide supportive care and corticosteroids as needed.
• Parkinsonism and Guillain-Barré Syndrome: Serious neurologic events including fatal cases have been reported.
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS): Potentially fatal hyperinflammatory conditions can overlap with CRS or neurologic toxicities.
• Prolonged/Recurrent Cytopenias: May require stem cell transplantation due to persistent low blood counts with bleeding or infection risks.
• Immune Effector Cell-associated Enterocolitis: Including life-threatening cases have been observed post-treatment.
• Secondary Hematological Malignancies: Including myelodysplastic syndrome, acute myeloid leukemia, or T-cell malignancies have occurred following treatment.

Common and Serious Adverse Reactions

The label details serious and life-threatening reactions such as Cytokine Release Syndrome, neurologic toxicities including ICANS, Parkinsonism, Guillain-Barré Syndrome, HLH/MAS, prolonged cytopenias, immune effector cell-associated enterocolitis, and secondary hematological malignancies. Close monitoring and readiness for prompt management of these effects are required. Specific incidence rates are not provided in the supplied label text.

Use caution with concomitant immunosuppressive agents as systemic corticosteroids may reduce CAR T-cell activity. Tocilizumab is recommended for treating CRS. No specific drug interaction details beyond treatment strategies are provided.

No pregnancy or lactation information is provided in the supplied evidence.

The label does not specify overdose symptoms or management.

Carvykti is shipped and stored in the vapor phase of liquid nitrogen. It must be thawed just before infusion and used within 2.5 hours at room temperature. Do not refreeze or refrigerate once thawed. Follow biosafety guidelines for handling genetically modified cells.