A Phase I clinical trial of chimeric antigen receptor-modified T cells in patients with relapsed and refractory lymphoma
A Phase I clinical trial of chimeric antigen receptor-modified T cells in patients with relapsed and refractory lymphoma
复制标题
嵌合抗原受体修饰 T 细胞治疗复发难治性淋巴瘤患者的 I 期临床试验
DOI：
10.2217/imt-2020-0022
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发表时间：
2020-07-01
期刊：
影响因子：
2.8
通讯作者：
Zhang, Yi
中科院分区：
文献类型：
--
作者：
Chen, Xinfeng;Li, Xin;Zhang, Yi
目的：CD19嵌合抗原受体(CAR)T细胞已被美国FDA批准用于治疗复发和难治性(R/R)B细胞恶性肿瘤。患者与方法：本研究探讨了自体4-1BB共刺激结构域工程CD19CAR-T细胞治疗R/R B细胞淋巴瘤的安全性和有效性。结果：CD19CAR-T细胞输注后，28.6%(4/14)的患者出现严重细胞因子释放综合征。总有效率为77%，3个月后6/14例患者完全缓解。化疗后肿瘤负担较重和3-4级骨髓抑制与严重的细胞因子释放综合征相关。值得注意的是，CD19 CAR-T细胞和PD-1阻断联合使用，而不是单独使用CD19 CAR-T细胞，可以减轻淋巴瘤中枢性侵袭患者的颅内肿瘤负担。结论：CD19CAR-T细胞可有效诱导肿瘤缓解，PD-1阻断可提高中国人R/R B细胞淋巴瘤的疗效。
Aim: CD19 chimeric antigen receptor (CAR) T cells have been approved by the US FDA for treatment of relapsed and refractory (R/R) B-cell malignancies. Patients & methods: This study investigated the safety and efficacy of autologous 4-1BB costimulatory domain-engineered CD19 CAR-T cells in R/R B-cell lymphoma. Results: After CD19 CAR-T-cell infusion, severe cytokine release syndrome occurred in 28.6% (4/14) of the patients. The overall response rate was 77% with complete remission observed in 6/14 patients at 3 months. A higher tumor burden and grade 3-4 of myelosuppression after chemotherapy were associated with severe cytokine-release syndrome. Notably, combining CD19 CAR-T cells and PD-1 blockade, but not CD19 CAR-T cells alone, reduced intracranial tumor burden in a patient with central invasion of lymphoma. Conclusion: CD19 CAR-T cells could effectively induce tumor remission and PD-1 blockade might improve the efficacy in Chinese patients with R/R B-cell lymphoma.