In preliminary efficacy results, treatment with a single low-dose infusion of ciltacabtagene autoleucel (cilta-cel) led to early, deep, and durable responses in patients with relapsed/refractory multiple myeloma (MM). Saad Usmani, MD, from Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, presented these findings as part of the 2021 ASCO Annual Meeting.
Cilta-cel is an autologous chimeric antigen receptor (CAR) T-cell therapy with two BCMA–targeting single-domain antibodies. The CARTITUDE-1 trial enrolled adults with MM who had received three or more prior regimens or who were double-refractory to an immunomodulatory drug (IMiD) and proteasome inhibitor (PI) and had received a PI, IMiD, and anti-CD38 antibody.
After apheresis and collection of cells to create the CAR T-cell product, patients underwent a three-day course of lymphodepletion with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2. Patients then received a single infusion of cilta-cel at a target dose of 0.75×106 cells/kg (range = 0.5-1.0×106 cells/kg) within seven days of completing lymphodepletion.
The goals of the first phase of the trial were to characterize the safety of cilta-cel and confirm the recommended phase II dose, Dr. Usmani explained. Efficacy was evaluated in the second phase.
At the time of data presentation, 97 of the 113 enrolled patients had received cilta-cel. The investigators noted that these patients had heavily pretreated MM, with a median of six prior lines of therapy (range = 3-18) prior to enrollment.
The overall response rate (ORR) was 97%, including a stringent complete response (sCR) rate of 67%. Responses appeared to occur rapidly, with a median time to first response of one month (range = 1-9) and a median time to CR of two months (range = 1-15).
Responses deepened over time, and the median duration of response was not reached after a median follow-up of 12.4 months.
The rate of 12-month progression-free survival (PFS) and overall survival (OS) were 77% and 89%, respectively, and the median PFS had not been reached at the time of presentation.
Among the 57 patients evaluable for measurable residual disease (MRD) assessment, 93% had MRD negativity at a level of 10-5.
The most commonly reported grade 3/4 hematologic adverse events (AEs) across the study population included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). Cytokine release syndrome (CRS) and neurotoxicity – both of which are commonly associated with CAR T-cell therapies – occurred in 95% and 21% of patients, respectively. The median time to CRS onset was seven days and the median duration was four days (range = 1-27); most cases resolved, except for one case of grade 5 CRS/hemophagocytic lymphohistiocytosis.
Fourteen patients died on study (5 due to progressive disease, 3 to AEs unrelated to treatment, and 6 to treatment-related AEs).
Although these findings need to be confirmed in larger trials with larger patient populations, these findings suggest that cilta-cel has promising efficacy compared with other CAR T-cell therapy candidates for MM.
Study authors report relationships with Janssen, which sponsored the trial.
Usmani SZ, Berdeja JG, Madduri D, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed/refractory multiple myeloma (R/R MM): Updated results from CARTITUDE-1. Abstract #8005. Presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021.