"CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma".The New England Journal of Medicine. 2019.

Clinical Question

Does the chimeric antigen receptor (CAR) T-cell therapy bb2121, which targets B-cell maturation antigen (BCMA), improve outcomes in patients with relapsed or refractory multiple myeloma?

Bottom Line

In patients with relapsed or refractory multiple myeloma, bb2121 CAR T-cell therapy resulted in an 85% objective response rate, with a median progression-free survival of 11.8 months. Toxicity was manageable, with mostly low-grade cytokine release syndrome and neurologic toxic effects.

Major Points

Multiple myeloma remains a disease with no curative treatment, and patients often experience relapse even after multiple lines of therapy. The CAR T-cell therapy bb2121 represents an innovative approach by redirecting the patient's own T cells to target BCMA, which is expressed on myeloma cells. This phase 1 study demonstrated substantial efficacy in a heavily pretreated population, with high response rates and durable remissions.

Guidelines

As of the knowledge cutoff date, no guidelines have been established for bb2121 in the context of relapsed or refractory multiple myeloma due to the novelty of the treatment.

Design

Open-label, phase 1, multicenter study with two parts: a dose-escalation phase and a dose-expansion phase.
N=33 patients who received bb2121.
Setting: Multiple centers in the United States.
Enrollment: 2016-2018.
Mean follow-up: 11.3 months.
Analysis: Intention-to-treat.
Primary outcome: Safety profile of bb2121 therapy.

Population

Inclusion Criteria:
- Age ≥18 years.
- Eastern Cooperative Oncology Group performance-status score of 0 or 1.
- Measurable disease with specific laboratory criteria.
- At least three previous lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or refractory to both drug classes.

Exclusion Criteria:
- Patients who did not meet the eligibility criteria based on their medical condition and prior treatments.

Baseline Characteristics
- Median age: 60 years (range, 37 to 75).
- Median time since diagnosis: 5 years (range, 1 to 36).
- Patients had received a median of 7 to 8 prior treatment regimens.

Interventions

- Single infusion of bb2121 with varying doses (50x10^6 to 800x10^6 CAR-positive [CAR+] T cells).
- Lymphodepletion with fludarabine and cyclophosphamide.

Outcomes

Primary Outcomes
- Safety: Hematologic toxic effects most common, including neutropenia (85%), leukopenia (58%), anemia (45%), and thrombocytopenia (45%).
- Cytokine release syndrome occurred in 25 patients (76%), mostly grade 1 or 2.
- Neurologic toxic effects occurred in 42% of patients, with one reversible grade 4 event.

Secondary Outcomes
- Objective response rate: 85%.
- Complete response rate: 45%.
- Median progression-free survival: 11.8 months.
- Persistence of CAR T cells was observed in 20% of patients at 12 months.

Criticisms

- Small sample size in this phase 1 study limits the generalizability of the results.
- Longer follow-up is required to determine long-term durability of responses and potential late toxic effects.

Funding

Supported by Bluebird Bio and Celgene.

Further Reading

The full text of this study can be found at NEJM.org.