bb2121 anti-BCMA CAR T-cell therapy in patients with relapsed/refractory multiple myeloma: Updated results from a multicenter phase I study.

8007 Background: bb2121 is a second-generation chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) to redirect T cells to recognize and kill malignant myeloma cells. Initial data from the dose-escalation (DE) phase of CRB-401, a first-in-human study of bb2121 in relapsed/refractory multiple myeloma (RRMM), have shown promising efficacy and safety. We report updated safety and efficacy results on 43 patients (pts) enrolled in this ongoing study. Methods: CRB-401 (NCT02658929) is a 2-part, phase I study of bb2121 in pts with RRMM. DE pts had received ≥ 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or were double refractory, and had ≥ 50% BCMA expression on plasma cells. In the dose-expansion (Exp) phase, pts had to have received daratumumab and been refractory to last line of therapy; no BCMA expression was required. Following lymphodepletion with Flu (30 mg/m2)/Cy (300 mg/m2) given daily for 3 days, pts received 1 infusion of bb2121. Results: As of 02 Oct 2017, 21 pts had received bb2121 in the 4 DE cohorts (median follow-up, 35 weeks); no DLTs and no grade ≥ 3 neurotoxicities (NTX) were observed. Cytokine release syndrome (CRS), primarily grade 1-2, was reported in 15 of 21 (71%) pts; 2 pts had grade ≥ 3 CRS that resolved in 24 hours. There were 2 deaths on study; both pts had achieved complete response (CR) and had not progressed. Overall response rate in the 18 evaluable pts in DE cohorts ≥ 150 × 106 CAR T cells was 94%; 10 of 18 (56%) pts had CR or unconfirmed CR; 9 of 10 evaluable pts were MRD-negative. With a median follow-up of 40 weeks in ≥ 150 × 106 DE cohorts, median response duration and progression-free survival (PFS) had not been reached; PFS rates at 6 and 9 months were 81% and 71%, respectively. Doses of 150 to 300 × 106 CAR T cells were selected for the Exp phase. Results from an additional 5 months of follow-up and initial data from ~20 pts from the Exp cohort will be presented. Conclusions: bb2121 shows promising efficacy at dose levels ≥ 150 × 106 CAR T cells with deep and durable ongoing responses and manageable CRS and NTX. These data support the potential of bb2121 anti-BCMA CAR T cell therapy as a new treatment paradigm for RRMM. Clinical trial information: NCT02658929.