Legend Biotech Corporation announced the U.S. Food and Drug Administration (FDA) has approved CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) for the treatment of patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor (PI), and an immunomodulatory agent (IMiD), and are refractory to lenalidomide. CARVYKTI® is the first and only B-cell Maturation Antigen (BCMA) targeted therapy, including CAR-T therapies, bispecific antibodies, and antibody-drug conjugates (ADCs), approved starting in the second-line of treatment for patients with multiple myeloma. The FDA approval is based on positive results from the CARTITUDE-4 study, which demonstrated that CARVYKTI® resulted in statistically significant and clinically meaningful improvement of progression-free survival compared to two standard of care treatment regimens, pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd), in adults with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.

This approval follows a unanimous (11 to 0) recommendation from the FDA Oncologic Drugs Advisory Committee (ODAC) in support of CARVYKTI® in earlier lines of treatment. The safety profile for CARVYKTI® includes a boxed warning for Cytokine Release Syndrome (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, and T-cell malignancies. Warnings and Precautions include Increased Early Mortality, Infections, Hypogammaglobulinemia, Hypersensitivity Reactions, and Effects on Ability to Drive and Use Machines.

The most common nonlaboratory adverse reactions (incidence greater than 20%) are 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 Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia.