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


Key Points

  • bb2121 is a CAR T-cell therapy targeting B-cell maturation antigen.
  • bb2121 is safe in patients with relapsed or refractory multiple myeloma.
  • Phase I study reported an objective response rate of 85%.

In a phase I trial reported in The New England Journal of Medicine, Raje et al found that bb2121, a chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA), was safe in heavily pretreated patients with relapsed or refractory multiple myeloma. Investigators reported an objective response rate of 85%.

Study Details

The U.S. multicenter study included patients who 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 current report provides data on the first 33 consecutive patients who received a bb2121 infusion.

Patients received single infusions at doses levels of 50×106, 150x106, 450x106, or 800×106 CAR-positive T cells in a dose-escalation phase (n = 21) and at 150×106 to 450×106 CAR-positive T cells in an expansion phase (n = 12). The median number of prior therapies was seven in the escalation cohort and eight in the expansion cohort.


Objective response was observed in 28 patients (85%), with complete response observed in 15 (45%). Median duration of response was 10.9 months. At the time of analysis, relapse had occurred in 6 of 15 patients with complete response. Median progression-free survival was 11.8 months. The 16 responders who were evaluated for minimal residual disease (MRD) had MRD-negative status (≤ 10-4 nucleated cells). CAR T-cells persisted up to 1 year after the infusion, and CAR T-cell expansion was associated with response.  


Hematologic toxicities were the most common adverse events of grade ≥ 3, including neutropenia (85%), leukopenia (58%), anemia (45%), and thrombocytopenia (45%). Cytokine release syndrome occurred in 25 patients (76%) and was of grade 3 in 2 (6%). Neurologic adverse events occurred in 14 patients (42%), with 1 patient having a grade 4 event.

The investigators concluded, “…In a heavily pretreated population of patients with multiple myeloma, bb2121 showed promising efficacy at dose levels of 150×106 or more CAR-positive T cells. Nonhematologic toxic effects were primarily of grade 2 or lower.”

Disclosure: The study was funded by Bluebird Bio and Celgene. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.