General Information

Carvykti (ciltacabtagene autoleucel; cilta-cel) is a chimeric antigen receptor T-cell (CAR-T) therapy featuring two B-cell maturation antigen (BCMA)-targeting single domain antibodies.

Carvykti is specifically indicated 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-CD38 monoclonal antibody.

Carvykti is supplied as a suspension for intravenous infusion. 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 0.5-1.0×106 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.

Carvykti is for autologous 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.

Confirm availability of Carvykti prior to starting the lymphodepleting chemotherapy regimen.

Administer Carvykti infusion 2 to 4 days after the completion of the lymphodepleting chemotherapy regimen.

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).

Mechanism of Action

Carvykti (ciltacabtagene autoleucel; cilta-cel) is a BCMA-directed, genetically modified autologous T cell immunotherapy, which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. The Carvykti  CAR protein features two BCMA-targeting single-domain antibodies designed to confer high avidity against human BCMA, a 4-1BB co-stimulatory domain and a CD3-zeta (CD3ζ) signaling cytoplasmic domain. Upon binding to BCMA-expressing cells, the CAR promotes T cell activation, expansion, and elimination of target cells.

Side Effects

Adverse effects associated with the use of Carvykti may include, but are not limited to, the following:

Pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.

The most common laboratory adverse reactions (incidence greater than or equal to 50%) include thrombocytopenia, neutropenia, anemia, aminotransferase elevation and hypoalbuminemia.

The Carvykti drug label comes with the following Black Box Warning: 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. 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. Parkinsonism and Guillain-Barré syndrome and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with Carvykti. 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. Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with Carvykti. Carvykti is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).

Clinical Trial Results

The approval was based on data from the pivotal CARTITUDE-1 study, which included patients who had received a median of six prior treatment regimens (range, 3-18), and had previously received a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. In the study, one-time treatment with ciltacabtagene autoleucel resulted in deep and durable responses, with 98 percent of patients with RRMM responding to therapy (98 percent overall response rate [ORR] (n=97). Of the patients achieving this level of response (n=76), 78% experienced a stringent complete response (sCR), a measure in which a physician is unable to observe any signs or symptoms of disease via imaging or other tests after treatment. At a median of 18 months follow-up, median duration of response (DOR) was 21.8 months.