Xue Bin, Liu Yifan, Li Bing, Lu Yan, Zhou Lili, Ye Shiguang, Lu Huina, Luo Xiu, Liang Aibin, Li Ping
Department of Hematology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Clinical Research Ward of Cancer Center, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Front Immunol. 2025 May 6;16:1582944. doi: 10.3389/fimmu.2025.1582944. eCollection 2025.
CD19 Chimeric Antigen Receptor T-cell therapy (CART) represents a groundbreaking approach in the treatment of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). However, a subset of patients fails to achieve optimal outcomes with CD19-targeted CAR T-cells alone. To address these limitations, the development of multi-targeted CART therapies has become a focal point of innovative research. This study aims to compare the therapeutic efficacy and adverse events of dual-target versus single-target CART therapies in R/R DLBCL patients through a single-center retrospective analysis.
We included 70 patients with R/R DLBCL treated at Shanghai Tongji Hospital between January 1, 2019, and December 31, 2021. Among them, 20 patients received dual-target (CD19/20) CART, while 50 underwent CD19 CART.
The CD19/20 CART group demonstrated significantly superior three-month efficacy to the CD19 CAR T-cell group, with a notably higher complete response (CR) rate. The median progression-free survival (PFS) and overall survival (OS) were 28.6 and 31.8 months longer in the Bi-CART group compared to the CD19 CAR T-cell group. However, the two groups had no significant differences in overall PFS, duration of response (DOR), or OS. The CD19/20 CART group exhibited a higher incidence of cytokine release syndrome (CRS), hematological toxicity, infections, and secondary primary tumors.
This study highlights the superior efficacy of dual-target CAR T-cell therapy in managing R/R DLBCL patients. The dual-target therapy significantly extended median survival compared to CD19 single-target CAR T-cell therapy. However, the enhanced therapeutic benefits were accompanied by a higher incidence of adverse effects.
CD19嵌合抗原受体T细胞疗法(CART)是治疗复发或难治性弥漫性大B细胞淋巴瘤(R/R DLBCL)的一种开创性方法。然而,一部分患者仅使用靶向CD19的CAR T细胞无法获得最佳疗效。为解决这些局限性,多靶点CART疗法的开发已成为创新研究的焦点。本研究旨在通过单中心回顾性分析比较双靶点与单靶点CART疗法在R/R DLBCL患者中的治疗效果和不良事件。
我们纳入了2019年1月1日至2021年12月31日期间在上海同济大学附属同济医院接受治疗的70例R/R DLBCL患者。其中,20例患者接受了双靶点(CD19/20)CART治疗,而50例接受了CD19 CART治疗。
CD19/20 CART组在三个月时的疗效明显优于CD19 CAR T细胞组,完全缓解(CR)率显著更高。与CD19 CAR T细胞组相比,双靶点CART组的中位无进展生存期(PFS)和总生存期(OS)分别长28.6个月和31.8个月。然而,两组在总体PFS、缓解持续时间(DOR)或OS方面无显著差异。CD19/20 CART组的细胞因子释放综合征(CRS)、血液学毒性、感染和继发性原发性肿瘤的发生率更高。
本研究突出了双靶点CAR T细胞疗法在治疗R/R DLBCL患者方面的卓越疗效。与CD19单靶点CAR T细胞疗法相比,双靶点疗法显著延长了中位生存期。然而,治疗益处的增强伴随着更高的不良反应发生率。