2018 ASCO Annual Meeting!
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Type: Oral Abstract Session
Time: Friday June 1, 2:45 PM to 5:45 PM
bb2121 anti-BCMA CAR T-cell therapy in patients with relapsed/refractory multiple myeloma: Updated results from a multicenter phase I study.
Hematologic Malignancies—Plasma Cell Dyscrasia
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 8007)
Author(s): Noopur S. Raje, Jesus G. Berdeja, Yi Lin, Nikhil C. Munshi, David Samuel DiCapua Siegel, Michaela Liedtke, Sundar Jagannath, Deepu Madduri, Jacalyn Rosenblatt, Marcela Valderrama Maus, Ashley Turka, Lyh Ping Lam, Richard A. Morgan, Travis Quigley, Monica Massaro, Kristen Hege, Fabio Petrocca, James Kochenderfer; Massachusetts General Hospital Cancer Center, Boston, MA; Sarah Cannon Research Institute, Nashville, TN; Mayo Clinic, Rochester, MN; Dana-Farber Cancer Institute, Boston, MA; Hackensack University Medical Center, Hackensack, NJ; Stanford University School of Medicine, Palo Alto, CA; Mount Sinai Medical Center, New York, NY; Beth Israel Deaconess Medical Center, Boston, MA; Bluebird Bio, Cambridge, MA; Celgene Corporation, Summit, NJ; Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD
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
2. Pomalidomide (POM), bortezomib, and low‐dose dexamethasone (PVd) vs bortezomib and low-dose dexamethasone (Vd) in lenalidomide (LEN)-exposed patients (pts) with relapsed or refractory multiple myeloma (RRMM): Phase 3 OPTIMISMM trial.