Dong Yetian, Yang Tingting, Zhao Mengyu, Song Fengmei, Chen Rongrong, Zhang Mingming, Hong Ruimin, Feng Jingjing, Fu Shan, Xiao Pingnan, Xu Huijun, Cui Jiazhen, Huang Simao, Wei Guoqing, Chang Alex H, Huang He, Hu Yongxian
Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
Institute of Hematology, Zhejiang University, Hangzhou, China.
Bone Marrow Transplant. 2025 Aug 20. doi: 10.1038/s41409-025-02691-2.
Chimeric antigen receptor (CAR)-T cells have made great progress in hematological malignancies and optimization of CAR structure is a critical area of exploration. Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). We conducted a clinical trial to determine the safety of hCART19 for patients with R/R B-NHL. Successful infusion of hCART19 were achieved for 26 patients. Twenty-one (80.8%) patients had grade 1-2 cytokine release syndrome (CRS), with only 1 patient having grade 3 CRS. Besides, no immune effector cell-associated neurotoxicity (ICANS) was observed among all the patients. Twenty-one (80.8%) patients achieved an objective response, including 18 (69.2%) complete remission (CR) and 3 (11.5%) partial remission (PR) within 1 month post-infusion. The other 5 patients acquired no response (NR). With a median follow-up time of 20.3 months, 77.8% (14/18) of the CR patients remained CR. The estimated 1-year OS and PFS were 65.8% (95% CI, 49.1% to 88.2%) and 54.8% (95% CI, 38.1% to 78.7%), respectively. CAR-T expansion was observed in all patients (median peak: 220.63 cells/µL). hCART19 demonstrated favorable efficacy and manageable toxicity in R/R B-NHL, providing critical clinical evidence for its clinical application.
嵌合抗原受体（CAR）-T细胞在血液系统恶性肿瘤治疗方面取得了重大进展，而CAR结构的优化是一个关键的探索领域。针对复发/难治性（R/R）B细胞非霍奇金淋巴瘤（B-NHL），评估人源化靶向CD19的CAR-T细胞（hCART19）的研究有限。我们开展了一项临床试验，以确定hCART19用于R/R B-NHL患者的安全性。26例患者成功输注了hCART19。21例（80.8%）患者发生1-2级细胞因子释放综合征（CRS），仅有1例患者发生3级CRS。此外，所有患者均未观察到免疫效应细胞相关神经毒性（ICANS）。21例（80.8%）患者获得客观缓解，包括输注后1个月内18例（69.2%）完全缓解（CR）和3例（11.5%）部分缓解（PR）。另外5例患者无反应（NR）。中位随访时间为20.3个月，77.8%（14/18）的CR患者仍处于CR状态。估计1年总生存率（OS）和无进展生存率（PFS）分别为65.8%（95%CI，49.1%至88.2%）和54.8%（95%CI，38.1%至78.7%）。所有患者均观察到CAR-T细胞扩增（中位峰值：220.63个细胞/µL）。hCART19在R/R B-NHL中显示出良好的疗效和可管理的毒性，为其临床应用提供了关键的临床证据。
