Ciltacabtagene autoleucel

Multiple myeloma is a malignancy involving the plasma cells of the bone marrow. It is a rare malignancy, with an estimated yearly incidence of 6.5 people per 100,000, and is variable in its presentation - some patients may remain entirely asymptomatic, while others may experience a range of symptoms including bone pain, hematologic abnormalities, and end-organ damage. There have been a number of treatments developed for multiple myeloma (e.g. daratumumab), although none are curative.

B-cell maturation antigen (BCMA) is a transmembrane glycoprotein member of the tumor necrosis factor receptor superfamily 17 (TNFRSF17) which is used as a biomarker for multiple myeloma. While normally expressed on plasma blasts and plasma cells, BCMA is widely expressed on malignant plasma cells and most multiple myeloma cell lines, making it a choice target in the development of immunotherapies against multiple myeloma.

Ciltacabtagene autoleucel (Carvykti, Jannsen Biotech Inc.) is a BCMA-directed genetically modified autologous T-cell immunotherapy. Patient T-cells are reprogrammed with a transgene encoding a specific chimeric antigen receptor (CAR) which features two BCMA-targeting single-domain antibodies. Re-infusion of these modified T-cells leads to the targeted elimination of malignant plasma cells, on which BCMA is highly expressed. Carvykti was first approved by the FDA in February 2022 for the treatment of relapsed or refractory multiple myeloma in treatment-experienced patients.