Dr. Xian Zhang’s Latest Research on BCMA CAR-T Therapy Published in Blood Advances

Introduction:
A recent breakthrough in the treatment of relapsed/refractory plasma cell myeloma (R/R MM) has been reported by Dr. Xian Zhang and his team at Ludaobei Hospital. Their clinical study on the efficacy and safety of BCMA nanobody CAR-T cell therapy in multi-line refractory plasma cell tumors was published in the prestigious journal Blood Advances. This novel treatment approach is gaining attention for its potential to significantly improve outcomes for patients who have limited options.

Background:
R/R MM patients, particularly those with extramedullary disease, central nervous system (CNS) involvement, or high-risk genetic abnormalities, have a poor prognosis. While BCMA CAR-T therapy has brought new hope for these patients, traditional CAR-T therapies face limitations such as antigen loss, immunogenicity, and insufficient persistence. This study focuses on a new dual-nanobody BCMA CAR-T therapy.

Study Design:
The study included 27 patients with complex, high-risk R/R plasma cell tumors, including 22 with multiple myeloma, 4 with plasma cell leukemia, and 1 with anaplastic plasma cell tumor. Among them, 11 had extramedullary disease (3 with CNS involvement) and 11 had high-risk genetic mutations (e.g., TP53 mutations). Patients received an infusion of BCMA CAR-T cells (1×10^6/kg). The primary endpoints were overall response rate (ORR) and safety, while secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Key Findings:

• The ORR at 3 months was 100%, with a complete response (CR) + very good partial response (VGPR) rate of 81.5%.

• The median DOR was 11 months (range: 2-36 months).

• In high-risk patients, the CR rate at 3 months was 72.7%, and the 1-year PFS was 65.5%.

• All 3 CNS patients achieved remission, with 2 reaching CR.

• For the anaplastic plasma cell leukemia patient, bone marrow MRD negativity was achieved and tumor shrinkage was observed.

Safety:
The treatment’s side effects were mainly mild cytokine release syndrome (CRS) and mild neurotoxicity, with infections being the primary complication, manageable with appropriate intervention.

Conclusion:
The dual-nanobody BCMA CAR-T therapy shows excellent efficacy and safety, particularly in high-risk patients. It offers promising results in treating R/R plasma cell tumors, providing hope for patients with complex disease. This study supports further optimization of BCMA CAR-T therapies and offers robust evidence for improving long-term outcomes for plasma cell myeloma patients.

Looking Ahead:
Ludaobei Hospital is one of the pioneers in BCMA CAR-T therapy in China, having completed over 100 cases. The team plans to continue advancing CAR-T research and explore combination therapies with stem cell transplants, antibody drugs, and small molecule inhibitors, to provide even more personalized, effective treatments for patients worldwide.