表达IL7和CCL19的第四代CD19 CAR-T联合PD-1单抗治疗复发难治大B细胞淋巴瘤的疗效和安全性

Efficacy and safety of fourth-generation CD19 CAR-T expressing IL7 and CCL19 along with PD-1 monoclonal antibody for relapsed or refractory large B-cell lymphoma

目的系统性研究表达白细胞介素7(IL7)和趋化因子C-C基序配体19(CCL19)的第四代靶向CD19嵌合抗原受体T细胞(CD19 CAR-T)联合PD-1单抗治疗复发难治大B细胞淋巴瘤的疗效及安全性。方法应用自体7×19 CAR-T联合替雷利珠单抗治疗11例复发难治大B细胞淋巴瘤患者,评估其疗效及不良反应。结果11例入组患者均完成自体7×19 CAR-T的制备和回输,9例患者完成预定的6次替雷利珠单抗治疗,1例患者完成4次,1例患者完成1次。5例(45.5%)达完全缓解,3例(27.3%)达部分缓解,客观缓解率72.7%。2例评估为疾病进展,1例在回输后2个月因疾病不能控制而死亡。中位随访时间31(2~34)个月,中位总生存时间未达到,中位无进展生存时间为28(1~34)个月,2例部分缓解患者分别在随访第9个月和第12个月进一步获得完全缓解,故最佳完全缓解率为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均可控,未见免疫相关不良反应发生。结论自体7×19 CAR-T联合替雷利珠单抗治疗复发难治大B细胞淋巴瘤取得较好疗效,且不良反应可控。

Objective This study systematically explore the efficacy and safety of fourthgeneration 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.Methods 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.Results 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 parial 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.Conclusion Autologous 7x19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.