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Published on: July 15, 2015
Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma
Noopur Raje1, Jesus Berdeja1, Yi Lin1
1From the Massachusetts General Hospital Cancer Center (N.R., M.V.M.), Beth Israel Deaconess Medical Center (J.R.), and Dana-Farber Cancer Institute and Veterans Affairs Boston Healthcare System (N.M.), Boston, and Bluebird Bio, Cambridge (A.T., L.-P.L., R.A.M., K.F., M.M., F.P., M.T.Q.) - all in Massachusetts; Sarah Cannon Research Institute and Tennessee Oncology, Nashville (J.B.); Mayo Clinic, Rochester, MN (Y.L.); Hackensack University Medical Center, Hackensack (D.S.), and Celgene, Summit (J.W., G.R., Z.Y.) - both in New Jersey; Mount Sinai Medical Center, New York (S.J., D.M.); Stanford University Medical Center, Palo Alto (M.L.), and Celgene, San Francisco (T.C., K.H.) - both in California; and the Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (J.N.K.).
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 ClinicalTrials.gov number, NCT02658929.).
Insights
This phase 1 study of bb2121 CAR T-cell therapy in multiple myeloma showed an 85% objective response rate. While toxicities like neutropenia and cytokine release syndrome occurred, antitumor activity was documented, warranting further investigation.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Preclinical data suggest bb2121, a chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA), shows promise for multiple myeloma treatment.
- Multiple myeloma is a cancer of plasma cells, often relapsing or refractory to standard therapies.
Purpose of the Study:
- To evaluate the safety and preliminary efficacy of bb2121 CAR T-cell therapy in patients with relapsed or refractory multiple myeloma.
- To determine the recommended dose for expansion studies.
Main Methods:
- A Phase 1 dose-escalation and expansion study of bb2121 in patients with relapsed/refractory multiple myeloma.
- Patients received bb2121 at doses ranging from 50x10^6 to 800x10^6 CAR-positive T cells.
- The primary endpoint was safety, with secondary endpoints including objective response rate and progression-free survival.
Main Results:
- An 85% objective response rate was observed in 33 patients, with 45% achieving complete responses.
- Common grade 3 or higher toxicities included neutropenia (85%), leukopenia (58%), anemia (45%), and thrombocytopenia (45%).
- Cytokine release syndrome occurred in 76% of patients (grade 3 in 6%), and neurologic events in 42% (grade 4 in 3%).
Conclusions:
- BCMA-directed CAR T-cell immunotherapy (bb2121) demonstrated significant antitumor activity in relapsed/refractory multiple myeloma.
- The initial toxicity profile was manageable, with documented CAR T-cell expansion and persistence.
- Further investigation is warranted to confirm efficacy and safety in this patient population.
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