CARVYKTI® Approved as First BCMA-Targeted Therapy for Relapsed/Refractory Multiple Myeloma After One Prior Line
Key Insights
CARVYKTI® (ciltacabtagene autoleucel) gains FDA approval for relapsed or refractory multiple myeloma (search) after just one prior line of therapy.
The approval is based on the Phase 3 CARTITUDE-4 study, which showed a 59% reduction in disease progression or death compared to standard therapies.
This approval expands access to CARVYKTI®, offering a potential treatment-free period for more patients with multiple myeloma (search) early in their treatment journey.
Johnson & Johnson's CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) has received FDA approval for the treatment of adult patients with relapsed or refractory multiple myeloma (search) who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. This approval marks CARVYKTI® as the first and only B-cell maturation antigen (BCMA (search))-targeted therapy for multiple myeloma patients as early as first relapse.
The FDA's decision is supported by data from the Phase 3 CARTITUDE-4 study, which demonstrated that CARVYKTI® significantly reduced the risk of disease progression or death by 59% compared to standard therapies—pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd)—in adults with relapsed and lenalidomide-refractory multiple myeloma (search) who had received one to three prior lines of therapy. The study was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine.
Clinical Impact and Expert Opinion
"CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma (search) as shown through the CARTITUDE-4 study results," said Binod Dhakal, M.D., Associate Professor, Medical College of Wisconsin, Division of Hematology and Oncology. "With this approval, I'm excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease."
Disease Burden and Treatment Landscape
In 2024, over 35,000 new cases of multiple myeloma (search), an incurable blood cancer, are estimated to be diagnosed in the United States. Real-world studies indicate that only about 15% of patients initially diagnosed with multiple myeloma are able to start a 5th line of therapy. This expanded indication for CARVYKTI® aims to provide more patients access to this innovative treatment option earlier in their disease progression.
CARVYKTI® Mechanism of Action
CARVYKTI® is a cell therapy that leverages a patient's own immune system, specifically T cells, to combat the disease. The process involves reprogramming the patient's T-cells with a transgene encoding a chimeric antigen receptor (CAR) that directs the CAR positive T cells to eliminate cells that express BCMA (search). BCMA is primarily expressed on the surface of malignant multiple myeloma (search) B-lineage cells, as well as late-stage B cells and plasma cells. The CARVYKTI® CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.
Manufacturing and Availability
Johnson & Johnson has been actively scaling up CARVYKTI® production since its initial approval in February 2022. "We understand the urgency for patients in need of CARVYKTI, and we have been making considerable progress in increasing supply and availability in anticipation of this milestone approval," said Tyrone Brewer, President, U.S. Hematology, Johnson & Johnson Innovative Medicine. The company more than doubled manufacturing of CARVYKTI® in 2023 and is striving to double it again in 2024.
Safety Profile
The safety profile for CARVYKTI® includes a boxed warning for Cytokine Release Syndrome (search) (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), Parkinsonism and Guillain-Barre syndrome and their associated complications, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), Prolonged and Recurrent Cytopenias and Secondary Malignancies including myelodysplastic syndrome, acute myeloid leukemia (search) and T-cell malignancies. Warnings and Precautions include Increased Early Mortality, Hypogammaglobulinemia, Infections, Hypersensitivity Reactions and Effects on Ability to Drive and Use Machines.