Clinical outcomes and spatial transcriptomic profiles of CD19/20 CAR-T therapy in relapsed or refractory B-cell non-Hodgkin's lymphoma

Clinical Snapshot

Key Findings

• P Value: Not reported for primary endpoints

• Effect Size: Complete remission rate 58%, partial response rate 16%

• Primary Outcome: Overall response rate of 74% (23/31 evaluable patients)

• Nnt Or Sensitivity: Number needed to treat approximately 1.4 for any response, 1.7 for complete remission

• Confidence Interval: Not reported

Clinical Application

Requires specialised CAR-T manufacturing capabilities and experienced treatment centres with intensive care support Would require TGA approval and PBS listing consideration. Currently, CD19 CAR-T therapies (tisagenlecleucel, axicabtagene ciloleucel) are PBS-listed for R/R DLBCL, providing precedent for reimbursement pathway Patients with relapsed/refractory B-cell NHL who have failed standard therapies, particularly those with normal LDH levels

Abstract

BACKGROUND: Relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma (B-NHL) remains a major therapeutic challenge despite CD19-directed chimeric antigen receptor (CAR) T-cell therapies, with treatment failure often driven by antigen escape and limited CAR-T persistence. Dual targeting of CD19 and CD20 may mitigate antigen loss. We conducted an expanded phase I/II study of bispecific CD19/20 CAR-T cells and incorporated spatially resolved single-cell transcriptomics to evaluate tumor-intrinsic and microenvironmental factors of clinical response. METHODS: Patients with R/R B-NHL received CD19/20 CAR-T cells following lymphodepletion. Efficacy, safety, CAR-T expansion/persistence, and B-cell reconstitution were assessed. Pretreatment tumor biopsies from five patients with divergent outcomes underwent spatial single-cell transcriptomic profiling. RESULTS: 32 patients were treated, including 24 with diffuse large B-cell lymphoma. Among 31 evaluable patients, the best overall response rate was 74%, including 58% achieving complete remission. Median progression-free and overall survival were 6.8 and 22.1 months, respectively. Response rates were higher in patients with normal lactate dehydrogenase. CAR-T expansion peaked on days 7-17, and persistence exceeded 500 days in long-term responders. Cytokine release syndrome occurred in 53% (12% grade ≥3) and immune effector cell-associated neurotoxicity syndrome in 9% (all grade 3), with no lasting deficits. Spatial profiling identified two dominant tumor architectures: (1) a B-cell-dominant phenotype, in which durable remission was associated with heightened apoptotic competence in malignant B cells, and (2) a fibroblast-enriched and monocyte/macrophage-enriched phenotype, in which response correlated with a chemokine-rich, T-cell-permissive microenvironment. CONCLUSIONS: Bispecific CD19/20 CAR-T therapy produced durable clinical activity with manageable toxicity. Spatial single-cell analysis reveals distinct tumor-intrinsic and microenvironmental features associated with CAR-T responsiveness, providing a spatially informed framework for understanding heterogeneous therapeutic outcomes. TRIAL REGISTRATION NUMBER: NCT04723914.

References

1. 1.Wang, L., Fang, C., Zheng, Y., Xu, Y., Huang, W., Zhao, W., Wang, Y., Xia, J., Tan, K., Wang, L., Peng, H., Guo, X., Wang, S., Wang, L., Liu, L., Qiao, J., Meng, X., He, Z., Wen, Z., Yu, C., Mei, J., Wang, H., Li, Y., & Yu, L. (2026). Clinical outcomes and spatial transcriptomic profiles of CD19/20 CAR-T therapy in relapsed or refractory B-cell non-Hodgkin's lymphoma. *Journal for Immunotherapy of Cancer*, *14*, Article 015114. https://doi.org/10.1136/jitc-2026-015114