First-in-Human Multicenter Study of bb2121 Anti-BCMA CAR T-Cell Therapy for RRMM: Updated Results
To examine the safety and efficacy of the chimeric antigen receptor (CAR) T-cell in relapsed/refractory multiple myeloma (RRMM), Berdeja and colleagues designed a second-generation CAR construct targeting B-cell maturation antigen (BCMA) to redirect T-cells to MM tumor cells. bb2121 consists of autologous T-cells transduced with a lentiviral vector encoding a novel CAR incorporating an anti-BCMA single-chain variable fragment, a 4-1BB co-stimulatory motif, and a CD3-zeta T-cell activation domain. This study reports the updated safety and efficacy results of this novel therapy.
The study, CRB-401, is a multicenter phase 1 dose-escalation trial of bb2121 in patients with RRMM who have received ≥3 prior regimens, including a proteasome inhibitor and an immunomodulatory agent, or are double-refractory, and have ≥50% BCMA expression on plasma cells. Peripheral blood mononuclear cells were collected via leukapheresis. Patients undergo lymphodepletion with fludarabine (30 mg/m2)/cytarabine (300 mg/m2) daily for 3 days, then receive 1 infusion of bb2121. The study follows a standard 3 + 3 design, with planned dose levels of 5, 15, 45, 80, and 120 x 107 CAR+ T-cells.
A total of 21 patients were infused with bb2121 in the first 4 dose cohorts, with a mean follow-up of 15.4 weeks. All 21 patients were refractory to both bortezomib and lenalidomide; the majority were also refractory to pomalidomide, carfilzomib, and daratumumab. As of data cutoff (May 2017), no dose-limiting toxicities have occurred, and the maximum tolerated dose of 80 x 107 CAR+ T-cells has been identified. Grade 1/2 cytokine release syndrome (CRS) was reported in 15 of 21 (71%) treated patients, including 2 patients with grade 3 CRS that resolved in 24 hours. In the 15 evaluable patients, the overall response rate was 100%, with 73% (n = 11) achieving very good partial response or better. CAR+ T-cell expansion was demonstrated consistently.
This study demonstrates that bb2121 shows promising efficacy, with mild and manageable adverse events in a heavily pretreated patient population. These initial data support the potential of CAR T-cell therapy with bb2121 as a new treatment paradigm in patients with RRMM.
Berdeja JG. ASCO Abstract 3010.