On February 28, 2022, ciltacabtagene autoleucel was approved for treatment of adults with relapsed or refractory multiple myeloma after at least four lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1
Ciltacabtagene autoleucel is a B-cell maturation antigen–directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using a patient’s own T cells, which are collected and genetically modified and infused back into the patient.
Ciltacabtagene autoleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy.
Supporting Efficacy Data
Approval was based on findings in the multicenter CARTITUDE-1 trial (ClinicalTrials.gov identifier NCT03548207). A total of 97 patients received a single infusion at 0.5 to 1.0 × 106 CAR-positive viable T cells/kg. A partial response or better was achieved in 95 patients (97.9%, 95% confidence interval [CI] = 92.7%–99.7%), and a stringent complete response occurred in 76 patients (78.4%); all patients with a complete response had a stringent complete response. Median time to first response was 1 month (range = 0.9–10.7 months). Median duration of response was 21.8 months (95% CI = 21.8 months to not estimable) among all responders and not estimable (95% CI = 21.8 months to not estimable) among those with a stringent complete response.
How It Is Used
Ciltacabtagene autoleucel is for autologous use only. It must be administered at a Risk Evaluation and Mitigation Strategy–certified health-care facility.
The recommended dose range for ciltacabtagene autoleucel is 0.5 to 1.0 × 106 CAR-positive viable T cells/kg, with a maximum dose of 1 × 108 CAR-positive viable T cells per single infusion. Product labeling provides instructions on administration of the cyclophosphamide/fludarabine lymphodepletion regimen and premedications and on management of cytokine-release syndrome and immune effector cell–associated neurotoxicity syndrome and other neurologic toxicity.
Among the 97 patients in the CARTITUDE-1 study, the most common adverse events of any grade were pyrexia (96%), cytokine-release syndrome (95%), hypogammaglobulinemia (94%), hypotension (51%), musculoskeletal pain (48%), fatigue (47%), and infection (41%). The most common grade 3 or 4 adverse events included infection (17%), pneumonia (11%), febrile neutropenia (10%), and hypotension (10%). Grade 3 or 4 cytopenias occurred in 63% to 99% of patients. Serious adverse events occurred in 55%, most commonly cytokine-release syndrome (21%), encephalopathy (10%), sepsis (7%), and pneumonia (7%). Fatal adverse events occurred in 9% of patients.
Ciltacabtagene autoleucel has a boxed warning for cytokine-release syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, immune effector cell–associated neurotoxicity syndrome, Parkinsonism and Guillain-Barré syndrome and their associated complications, and prolonged or recurrent cytopenia, all of which can be fatal or life-threatening.
Ciltacabtagene autoleucel also has warnings/precautions for prolonged and recurrent cytopenias, infections, hypogammaglobulinemia, hypersensitivity reactions, secondary malignancies, and effects on the ability to drive and use machines.
1. Carvykti (ciltacabtagene autoleucel) suspension for intravenous infusion prescribing information, Janssen Biotech, Inc., February 2022. Available at https://www.fda.gov/media/156560/download. Accessed on March 10, 2022.