替雷利珠单抗增强 CD19/22 双靶向 CAR-T 细胞在晚期复发/难治性 B 细胞非霍奇金淋巴瘤中的疗效

Dual-targeted chimeric antigen receptor T (CAR-T) cell is an important strategy to improve the efficacy of CD19 CAR-T cell against refractory or relapsed B cell non-Hodgkin lymphoma (R/R B-NHL).

However, durable responses are not achieved in most patients, in part owing CAR-T cell exhaustion caused by PD-1/PD-L1 pathway.

We conducted a prospective, single-arm study of dual-targeted CD19/22 CAR-T cell combined with anti-PD-1 antibody, tislelizumab, in R/R B-NHL (NCT04539444). Tislelizumab was administrated on +1 day after patients received infusion of CD19/22 CAR-T cell. Responses, survival and safety were evaluated. From 1 August 2020 to 30 March 2023, 16 patients were enrolled. The median follow-up time is 16. 0 (range: 5. 0-32. 0 months) months.

Overall response was achieved in 14 of 16 (87. 5%) patients, and the complete response (CR) was achieved in 11 of 16 (68. 8%) patients. The 1-year progression-free survival and overall survival rates were 68. 8% and 81. 3%, respectively. Of the 14 patients responded, 9 patients maintained their response until the end of follow-up. Among the 15 out of 16 (93.

8%) patients who had extranodal involvement, 14 (93. 3%) patients achieved overall response rate with 11 (73. 3%) patients achieving CR. Eight (50%) patients experienced cytokine release syndrome. No neurologic adverse events were reported. Gene Ontology-Biological Process enrichment analysis showed that immune response-related signaling pathways were enriched in CR patients.

Our results suggest that CD19/22 CAR-T cell combined with tislelizumab elicit a safe and durable response in R/R B-NHL and may improve the prognosis of those patients.