Anti-BCMA CAR T-Cell Therapy in Relapsed or Refractory Multiple Myeloma
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.
Response
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.
Toxicity
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 nejm.org.
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