Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma

Noopur Raje, Jesus Berdeja, Yi Lin, David Siegel, Sundar Jagannath, Deepu Madduri, Michaela Liedtke, Jacalyn Rosenblatt, Marcela V. Maus, Ashley Turka, Lyh Ping Lam, Richard A. Morgan, Kevin Friedman, Monica Massaro, Julie Wang, Greg Russotti, Zhihong Yang, Timothy Campbell, Kristen Hege, Fabio PetroccaM. Travis Quigley, Nikhil Munshi, James N. Kochenderfer

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132 Scopus citations

Abstract

BACKGROUND Preclinical studies suggest that bb2121, a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA), has potential for the treatment of multiple myeloma. METHODS In this phase 1 study involving patients with relapsed or refractory multiple myeloma, we administered bb2121 as a single infusion at doses of 50×10 6 , 150×10 6 , 450×10 6 , or 800×10 6 CAR-positive (CAR+) T cells in the dose-escalation phase and 150×10 6 to 450×10 6 CAR+ T cells in the expansion phase. Patients had received at least three previous lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or were refractory to both drug classes. The primary end point was safety. RESULTS Results for the first 33 consecutive patients who received a bb2121 infusion are reported. The data-cutoff date was 6.2 months after the last infusion date. Hematologic toxic effects were the most common events of grade 3 or higher, including neutropenia (in 85% of the patients), leukopenia (in 58%), anemia (in 45%), and thrombocytopenia (in 45%). A total of 25 patients (76%) had cytokine release syndrome, which was of grade 1 or 2 in 23 patients (70%) and grade 3 in 2 patients (6%). Neurologic toxic effects occurred in 14 patients (42%) and were of grade 1 or 2 in 13 patients (39%). One patient (3%) had a reversible grade 4 neurologic toxic effect. The objective response rate was 85%, including 15 patients (45%) with complete responses. Six of the 15 patients who had a complete response have had a relapse. The median progression-free survival was 11.8 months (95% confidence interval, 6.2 to 17.8). All 16 patients who had a response (partial response or better) and who could be evaluated for minimal residual disease (MRD) had MRD-negative status (≤10 −4 nucleated cells). CAR T-cell expansion was associated with responses, and CAR T cells persisted up to 1 year after the infusion. CONCLUSIONS We report the initial toxicity profile of a BCMA-directed cellular immunotherapy for patients with relapsed or refractory multiple myeloma. Antitumor activity was documented.

Original languageEnglish (US)
Pages (from-to)1726-1737
Number of pages12
JournalNew England Journal of Medicine
Volume380
Issue number18
DOIs
StatePublished - May 2 2019

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ASJC Scopus subject areas

  • Medicine(all)

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Raje, N., Berdeja, J., Lin, Y., Siegel, D., Jagannath, S., Madduri, D., Liedtke, M., Rosenblatt, J., Maus, M. V., Turka, A., Lam, L. P., Morgan, R. A., Friedman, K., Massaro, M., Wang, J., Russotti, G., Yang, Z., Campbell, T., Hege, K., ... Kochenderfer, J. N. (2019). Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. New England Journal of Medicine, 380(18), 1726-1737. https://doi.org/10.1056/NEJMoa1817226