CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD19 CAR-T 治疗复发/难治性 B 细胞非霍奇金淋巴瘤的长期随访：Ki-67 作为持续缓解的预后因素
英文原题：Long-Term Follow-Up of CD19 CAR-T for R/R B-NHL: Ki-67 as a Prognostic Factor for Sustained Remission.
查看英文原题
Long-Term Follow-Up of CD19 CAR-T for R/R B-NHL: Ki-67 as a Prognostic Factor for Sustained Remission.
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中文摘要
复发/难治性 B 细胞非霍奇金淋巴瘤（R/R B-NHL）患者通常预后不佳。尽管 CD19 CAR-T 细胞疗效显著，但影响其长期疗效的因素仍不清楚。研究者回顾性分析了本中心 79 名接受 CD19 CAR-T 治疗的 R/R B-NHL 患者，评估疗效、长期生存和预后因素。在所有可评估患者中，总缓解率为 89.7%；3 年缓解持续时间（DOR）为 44.9%（95% CI：34.2%–59.0%），3 年无进展生存期（PFS）为 40.2%（95% CI：30.3%–53.4%），3 年总生存期（OS）为 48.3%（95% CI：38.0%–61.3%）。长期不良事件包括低丙种球蛋白血症（74 名可评估患者中 73 人，92.4%）、病毒再激活（5.1%）和继发恶性肿瘤（5.1%）。
值得注意的是，肿瘤 Ki-67 高表达（>60%）与 CAR-T 细胞扩增峰值较低（P<0.01）、第 0 至 28 天扩增曲线下面积较小（P<0.0001），以及完全缓解率、DOR 和 PFS 较差（均 P<0.05）相关。但 CAR-T 细胞持续存在与长期缓解或生存无显著关联（均 P>0.05）。
总之，CD19 CAR-T 为 R/R B-NHL 患者带来持久缓解，长期不良事件可管理。肿瘤 Ki-67 高表达是预后不良因素，并与 CAR-T 扩增受限相关；CAR-T 细胞持续性则不影响长期预后。
展开英文摘要原文
Patients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) typically experience dismal outcomes. Although CD19 chimeric antigen receptor T-cell (CAR-T) therapy has shown considerable efficacy, the factors influencing its long-term efficacy remain unclear.
We retrospectively analyzed 79 R/R B-NHL patients treated with CD19 CAR-T cell therapy at our center to evaluate efficacy, long-term survival, and prognostic factors. Among all evaluable patients, the overall response rate was 89. 7%, with a 3-year duration of response (DOR) of 44. 9% (95% CI, 34. 2%-59.
0%), a 3-year progression-free survival (PFS) of 40. 2% (95% CI, 30. 3%-53. 4%), and a 3-year overall survival (OS) of 48. 3% (95% CI, 38. 0%-61. 3%). Long-term adverse events (AEs) included hypogammaglobulinemia, which occurred in 73 of 74 evaluable patients (92. 4%), viral reactivation (5. 1%), and secondary malignancy (5. 1%).
Notably, high tumor Ki-67 (>60%) was associated with lower peak CAR-T cell expansion (P < . 01), reduced area under the curve of expansion from day 0 to 28 (P < . 0001), and inferior complete response rate, DOR, and PFS (all P < . 05).
However, CAR-T cell persistence was not significantly associated with long-term remission or survival (all P > . 05).
In conclusion, CD19 CAR T cell therapy yielded sustained remissions in patients with R/R B-NHL, with manageable long-term AEs. High tumor Ki 67 expression serves as a poor prognostic factor and is linked to limited CAR T cell expansion, whereas CAR T cell persistence does not influence long-term prognosis.
论文信息
- 作者
- Yu Y、Wang W、Mo Z、Teng Y、Zhang M、Wang D、Fu S、Cui J
- 第一作者单位
- Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310003, China; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, 310003, China.China
- 通讯作者单位
- Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310003, China; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, 310003, China. Electronic address: weiguoqing2018@zju.edu.cn.China
- 期刊
- Transplantation and cellular therapy2026 Aug
- 原文标识
- PubMed 42134593 · DOI 10.1016/j.jtct.2026.05.010