The FDA has approved ciltacabtagene autoleucel (Carvykti), a CAR T-cell therapy, for adult patients with multiple myeloma that is refractory or has relapsed after four or more prior lines of therapy. This approval marks a significant advancement in the treatment landscape for patients with advanced multiple myeloma who have exhausted other treatment options.
The approval was based on the results of the CARTITUDE-1 clinical trial, which evaluated the efficacy and safety of cilta-cel in patients with relapsed or refractory multiple myeloma. The study demonstrated that a single infusion of cilta-cel resulted in a 98% overall response rate, with 78% of patients achieving a stringent complete response, meaning no signs of cancer were detected in their bone marrow or blood. The median duration of response was 22 months.
Clinical Efficacy and Impact
According to Dr. Sundar Jagannath, lead investigator of the CARTITUDE-1 trial, the response rates observed with cilta-cel are unprecedented compared to other approved drugs for multiple myeloma, which typically have response rates around 30%. Dr. Faith Davies of NYU Langone Health's Perlmutter Cancer Center emphasized the importance of having another therapeutic approach that works differently from standard treatments, offering a way to kill drug-resistant myeloma cells.
Mechanism of Action
Cilta-cel is a CAR T-cell therapy that targets the B-cell maturation antigen (BCMA), a protein found on multiple myeloma cells. The patient's own immune cells are collected and genetically modified to express a CAR that recognizes and binds to BCMA, enabling the T cells to target and kill myeloma cells. Cilta-cel differs from the first approved CAR T-cell therapy for multiple myeloma, idecabtagene vicleucel (Abecma), in that its CAR T cells bind to two sections of BCMA rather than one.
Side Effects and Management
Common side effects associated with cilta-cel include cytokine release syndrome (CRS), infections, and nerve problems such as neuropathy. In the CARTITUDE-1 trial, 95% of patients experienced CRS, but most cases were mild and manageable with steroids or other medicines. There is a boxed warning for potentially life-threatening side effects, including HLH/MAS, Guillain-Barre syndrome, parkinsonism, severe CRS, prolonged cytopenia, and ICANS. Healthcare providers are trained to manage these side effects, and safety has improved with increased experience.
Availability and Cost
Cilta-cel is currently available at a limited number of certified hospitals, and Janssen Pharmaceutical is working to expand availability as production scales up. The list price for a one-time infusion of cilta-cel is $465,000, but the final cost to patients will depend on their insurance coverage.
Future Directions
While cilta-cel has shown remarkable efficacy in heavily pre-treated patients, researchers are exploring its potential use earlier in the disease course. Dr. Davies suggests that using CAR T-cell therapies earlier, when patients' immune systems are less compromised, could lead to better and longer-lasting responses, potentially even cures. Clinical trials are underway to evaluate the efficacy and safety of cilta-cel in newly diagnosed patients with multiple myeloma.
