2018 ASCO Annual Meeting!
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Type: Poster Session
Time: Monday June 4, 8:00 AM to 11:30 AM
Location: Hall A
Early MRD negativity to predict deepening myeloma response in relapsed/refractory multiple myeloma (RRMM) patients treated with bb2121 anti-BCMA CAR T cells.
Hematologic Malignancies—Plasma Cell Dyscrasia
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #33)
J Clin Oncol 36, 2018 (suppl; abstr 8024)
Author(s): Nikhil C. Munshi, Jesus G. Berdeja, Yi Lin, James Kochenderfer, Noopur S. Raje, Michaela Liedtke, Sundar Jagannath, Deepu Madduri, Jacalyn Rosenblatt, Marcela Valderrama Maus, Ashley Turka, Lyh Ping Lam, Kristen Hege, Timothy Brandon Campbell, Monica Massaro, Fabio Petrocca, David Samuel DiCapua Siegel; Dana-Farber Cancer Institute, Boston, MA; Sarah Cannon Research Institute, Nashville, TN; Mayo Clinic, Rochester, MN; Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD; Massachusetts General Hospital Cancer Center, Boston, MA; 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; Hackensack University Medical Center, Hackensack, NJ
Background: A high frequency of rapid minimal residual disease-negative (MRD-neg) responses has been seen in CRB-401, a phase I trial of bb2121 CAR T cell therapy for RRMM (Kochenderfer, ASH 2017). We report IMWG responses in MRD-neg patients (pts) and associated factors. Methods: Pts treated with ≥ 150 × 106 BCMA CAR+ T cells in the dose-escalation phase of CRB-401 and evaluable for MRD by Adaptive NGS-based MRD Assay (Adaptive Biotechnologies) were included in this analysis (n = 10 as of 02 Oct 2017; median follow-up: 34 wks; min, max: 7, 67). Results: Nine of 10 evaluable pts were MRD-neg with a sensitivity of 1 in 10-4 nucleated cells (1 pt), 1 in 10-5 (6 pts), and 1 in 10-6 (2 pts). Achievement of MRD negativity was independent of depth of response at first MRD-neg assessment; 2 pts had stable disease, 3 had PR, 2 had VGPR, and 2 had CR / stringent CR. Of 8 evaluable MRD-neg pts, all showed ≥ 85% and ≥ 97% decline in serum BCMA and involved free light-chain levels, respectively, at month (M) 1. Two of 9 MRD-evaluable pts were in CR at MRD-neg assessment and the remaining 7 achieved deeper response over time, 4 with CR or stringent CR, 2 with VGPR and 1 with PR between M1 and M15. One MRD-neg pt became MRD-positive at M12, and 1 MRD-neg pt had progressed as of data cut-off. Achievement of MRD negativity was independent of occurrence of cytokine release syndrome. MRD-neg was observed across all active bb2121 doses (150 [n = 3], 450 [n = 5], and 800 x 106 [n = 1] CAR+ T cells). Of 9 MRD-neg pts, 7 had at least 6M follow-up and 1 had IMWG progression (at M6); 3 had at least 12M follow-up, 1 had become MRD-positive and none had IMWG progression. Attainment of MRD-neg was independent of peak CAR T expansion (vector copy min, max: 93,744, 1,457,070 copies/µg gDNA; n = 9) and was observed in high ( > 50%) bone marrow plasma cells (BMPC; n = 6) and low BMPC (n = 3) tumor burden pts. Eight of 9 MRD-neg pts had cytogenetic abnormalities including del(17), del(13), amp(1q21), or t(11;14). Conclusions: bb2121 induced a high frequency of rapid MRD-neg response, independent of IMWG MM responses. These early MRD-neg responses starting at M1 offer insights into bb2121 kinetics and may portend achievement of deeper responses over time. 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.