CARTITUDE-1 Trial: Targeting BCMA With CAR T-Cell Therapy for Myeloma
Posted: Friday, July 30, 2021
Infusion of a single dose of ciltacabtagene autoleucel, a chimeric antigen receptor (CAR) T-cell therapy, resulted in early, deep, and durable responses among patients with multiple myeloma who were heavily pretreated, according to study authors. Ciltacabtagene autoleucel is a CAR construct that has two different B-cell maturation antigen (BCMA)-targeting single-domain antibodies that are designed to confer avidity. The results of this trial were published in The Lancet by Sundar Jagannath, MBBS, of Mount Sinai Medical Center in New York, and colleagues.
This phase Ib/II study enrolled 113 patients with multiple myeloma across 16 different cancer centers in the United States. These patients had either received three or more previous lines of therapy or were double refractory to both a proteasome inhibitor and an immunomodulatory drug. Patients underwent lymphodepletion, followed by administration of a single ciltacabtagene autoleucel infusion at a target dose of 0.75 x 106 CAR-positive T cells/kg.
After a median follow-up of 12.4 months, 97 patients had received the ciltacabtagene autoleucel infusion at the target dose. The overall response rate was 97%, and 67% of patients achieved a stringent complete response. Among the patients who achieved a complete response, 62% did so within 3 months of treatment. The progression-free survival was not yet reached; however, the 12-month progression-free survival rate was 77%. The 12-month overall survival rate was 89%.
The most common grade 3 or 4 hematologic adverse events included neutropenia (95% of patients), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). Cytokine-release syndrome occurred in 95% of patients, with a median time to onset of 7 days and a median duration of 4 days. However, all patients but one had resolution of cytokine-release syndrome, and this patient developed hemophagocytic lymphohistiocytosis. Of the 14 deaths reported in the study, 6 were the result of treatment-related adverse events.
Disclosure: For a full list of author disclosures, visit thelancet.com.