Novel CAR T-Cell Therapy Active in Relapsed, Refractory Multiple Myeloma
Administration of bb2121, a novel anti–B-cell maturation antigen CAR T-cell therapy, produced anti-tumor responses in heavily pretreated patients with relapsed/refractory multiple myeloma, according to interim data from a phase I trial.
Administration of bb2121, a novel anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy, produced anti-tumor responses in heavily pretreated patients with relapsed/refractory multiple myeloma, according to interim data from an on-going phase I clinical trial.
Data from the trial were presented by Yi Lin, MD, PhD, assistant professor of medicine and oncology at the Mayo Clinic in Rochester, Minnesota, at the 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany.
According to the study abstract, previous studies of CAR T-cell therapies have shown robust and sustained clinical responses in several hematologic malignancies. With this study, Lin and colleagues tested the potential for CAR T-cell safety and efficacy in patients with relapsed/refractory multiple myeloma.
In order to redirect T cells to multiple myeloma, the researchers targeted BCMA, a member of the tumor necrosis factor superfamily that is near-uniformly expressed by malignant myeloma cells, plasma cells, and some mature B cells. The investigational drug, bb2121, consists of autologous T cells transduced with a lentiviral vector that encodes a novel CAR incorporating an anti-BCMA single-chain variable fragment, a 4-1BB costimulatory motif, and a CD3-zeta T-cell activation domain.
In the study, patients received a conditioning regimen of cyclophosphamide and fludarabine followed by an infusion of bb2121 anti-BCMA CAR T cells. Eleven patients have been enrolled and dosed into four cohorts: 5 × 107, 15 × 107, 45 × 107, and 80 × 107 CAR+ T cells. The CAR T cells were produced from each patient’s own blood cells, which were modified using the lentiviral vector encoding the anti-BCMA CAR. The primary endpoint of the study was incidence of adverse events and abnormal laboratory test results, including dose-limiting toxicities.
All patients in the trial were heavily pretreated with a median of 6 prior therapies. All patients had prior autologous stem cell transplant. The safety analysis included results from all 11 patients, and the efficacy analysis included results from the first 9 patients who have undergone tumor restaging.
Of the three patients dosed at 5 × 107 the overall response rate was 33% with 1 patient achieving a partial response and 1 patient achieving stable disease. At the 15 × 107 dose (cohort 2), the overall response rate was 100%. Two patients at this dose achieved stringent complete response and one achieved very good partial response. At the 45 × 107 dose (cohort 3), there was also a 100% overall response rate, with all three patients achieving partial remission. The overall response rate for all three cohorts was 78%. All patients in cohorts 2 and 3 with bone marrow involvement at baseline had no detectable multiple myeloma cells in their bone marrow on day 14 or beyond.
No dose-limiting toxicities had occurred at data cutoff. In addition, there were no grade 3 or higher neurotoxicities or cytokine release syndrome.
