Yu T, Liu H, Lei W, Chen P P, Zhao A Q, Yuan X G, Gao J M, Qian W B
Department of Hematology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.
Wenzhou Medical University Laboratory Medicine, Wenzhou 325035, China.
Zhonghua Xue Ye Xue Za Zhi. 2023 Oct 14;44(10):820-824. doi: 10.3760/cma.j.issn.0253-2727.2023.10.005.
This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Our center applied autologous 7×19 CAR-T combined with tirelizumab to treat 11 patients with relapsed or refractory large B-cell lymphoma. The efficacy and adverse effects were explored. All 11 enrolled patients completed autologous 7×19 CAR-T preparation and infusion. Nine patients completed the scheduled six sessions of tirolizumab treatment, one completed four sessions, and one completed one session. Furthermore, five cases (45.5%) achieved complete remission, and three cases (27.3%) achieved partial remission with an objective remission rate of 72.7%. Two cases were evaluated for disease progression, and one died two months after reinfusion because of uncontrollable disease. The median follow-up time was 31 (2-34) months, with a median overall survival not achieved and a median progression-free survival of 28 (1-34) months. Two patients with partial remission achieved complete remission at the 9th and 12th months of follow-up. Therefore, the best complete remission rate was 63.6%. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.
本研究系统地探讨了表达白细胞介素7(IL7)和趋化因子C-C基序配体19(CCL19)且靶向CD19的第四代嵌合抗原受体T细胞(CAR-T)在复发或难治性大B细胞淋巴瘤中的疗效和安全性。我们中心应用自体7×19 CAR-T联合替雷利珠单抗治疗11例复发或难治性大B细胞淋巴瘤患者。对疗效和不良反应进行了探讨。所有11例入组患者均完成了自体7×19 CAR-T的制备和输注。9例患者完成了预定的6个疗程的替雷利珠单抗治疗,1例完成了4个疗程,1例完成了1个疗程。此外,5例(45.5%)达到完全缓解,3例(27.3%)达到部分缓解,客观缓解率为72.7%。2例患者评估为疾病进展,1例在再次输注后2个月因疾病无法控制死亡。中位随访时间为31(2-34)个月,中位总生存期未达到,中位无进展生存期为28(1-34)个月。2例部分缓解患者在随访第9个月和第12个月时达到完全缓解。因此,最佳完全缓解率为63.6%。细胞因子释放综合征和免疫效应细胞相关神经毒性综合征可控,未发生免疫相关不良反应。自体7×19 CAR-T联合替雷利珠单抗治疗复发或难治性大B细胞淋巴瘤疗效良好,不良反应可控。