At the 2025 American Society of Hematology (ASH) Annual Meeting, researchers from Shenzhen University General Hospital presented updated results from a Phase I/II clinical trial evaluating bispecific CD19/CD20 CAR-T cell therapy in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. The study highlights encouraging response rates, durable disease control, and a manageable safety profile, reinforcing the potential of dual-target CAR-T strategies in overcoming antigen escape in high-risk lymphoma.
Abstract No.: abs25-12414
Abstract Title: Updated clinical outcomes of a Phase I/II trial of bispecific CD19/CD20-targeted CAR-T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma
Background
Non-Hodgkin lymphoma (NHL) is a common hematologic malignancy. For patients with relapsed or refractory (R/R) disease—particularly those with diffuse large B-cell lymphoma (DLBCL)—treatment options remain limited. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising immunotherapeutic approach for R/R hematologic malignancies. However, relapse after CAR-T therapy still occurs, often due to loss of CAR-T cell persistence or antigen escape. One strategy to overcome antigen loss is simultaneous targeting of multiple antigens. Tandem CAR-T cells targeting CD19 and CD22 have demonstrated encouraging efficacy in R/R B-cell acute lymphoblastic leukemia (B-ALL). Previously, our group reported promising results from a Phase I/II trial (n=11) of bispecific CD19/CD20 CAR-T cells in patients with R/R B-cell malignancies.
Methods
An updated analysis was conducted of an open-label, single-arm Phase I/II clinical trial evaluating bispecific CD19/CD20 CAR-T cell therapy in patients with R/R NHL treated at our center between May 2021 and November 2024. The primary endpoint was safety. Secondary endpoints included overall response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS).
Results
In this updated analysis, 32 patients with R/R NHL—including 27 patients with DLBCL—received lymphodepleting chemotherapy followed by infusion of CD19/CD20 CAR-T cells at doses ranging from 0.3×10⁶ to 2.7×10⁶ cells/kg.
- Best overall response rate (ORR): 77%
- Complete response (CR) rate: 60%
With a median follow-up of 12.6 months, the median PFS was 6.8 months (95% CI, 3.9 to not reached).
Cytokine release syndrome (CRS) occurred in 17 patients (53%), including:
- 41% grade 1–2 CRS
- 12% grade ≥3 CRS
Immune effector cell–associated neurotoxicity syndrome (ICANS) was observed in 3 patients (9%).
Conclusion
These findings support the potential of bispecific CD19/CD20 CAR-T cell therapy to induce durable remissions in patients with R/R NHL, with a manageable safety profile characterized by a moderate incidence of CRS and a low rate of neurotoxicity.
