On February 28, the U.S. Food and Drug Administration (FDA) approved ciltacabtagene autoleucel (Carvykti) for the treatment of adults 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. Ciltacabtagene autoleucel is a chimeric antigen receptor T-cell therapy featuring two B-cell maturation antigen–targeting single domain antibodies.
The approval is 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 pivotal CARTITUDE-1 study, one-time treatment with ciltacabtagene autoleucel resulted in deep and durable responses, with 98% (95% confidence interval [CI] = 92.7%–99.7%) of patients with relapsed or refractory multiple myeloma responding to therapy. Notably, 78% (95 % CI = 68.8%–86.1%) of the patients achieving this level of response (n = 76) experienced a stringent complete response, 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 was 21.8 months.
Ciltacabtagene autoleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI REMS Program. The safety information for ciltacabtagene autoleucel includes a boxed warning regarding cytokine-release syndrome, immune effector cell–associated neurotoxicity syndrome, Parkinsonism and Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged and/or recurrent cytopenias. Warnings and precautions include prolonged and recurrent cytopenias, infections, hypogammaglobulinemia, hypersensitivity reactions, secondary malignancies, and effects on ability to drive and use machines. The most common adverse reactions (≥ 20%) are pyrexia, cytokine-release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections–pathogens unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.
As a personalized medicine, ciltacabtagene autoleucel treatment requires extensive training, preparation, and certification to ensure a positive experience for patients. Through a phased approach, the manufacturer will activate a limited network of certified treatment centers as the company works to scale its production capacity and increase the availability of ciltacabtagene autoleucel throughout the United States.