Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma

N Engl J Med. 2019 May 2;380(18):1726-1737. doi: 10.1056/NEJMoa1817226.


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 50×106, 150×106, 450×106, or 800×106 CAR-positive (CAR+) T cells in the dose-escalation phase and 150×106 to 450×106 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. (Funded by Bluebird Bio and Celgene; CRB-401 number, NCT02658929.).

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Cell Maturation Antigen / antagonists & inhibitors*
  • CD4-CD8 Ratio
  • Female
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Multiple Myeloma / immunology
  • Multiple Myeloma / therapy*
  • Progression-Free Survival
  • Receptors, Chimeric Antigen / therapeutic use*
  • T-Lymphocytes / metabolism


  • B-Cell Maturation Antigen
  • Receptors, Chimeric Antigen
  • TNFRSF17 protein, human

Associated data