Zhou Wenyujing, Chen Weihong, Wan Xiaochun, Luo Changru, Du Xin, Li Xiaoqing, Chen Qian, Gao Ruiwen, Zhang Xiaohan, Xie Mei, Wang Mingjun
Department of Hematology, The First Affiliated Hospital of Shenzhen University/Shenzhen Second People's Hospital, Shenzhen, China.
Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Front Genet. 2022 Jan 20;12:815679. doi: 10.3389/fgene.2021.815679. eCollection 2021.
The aim was to study the benefits and risks of anti-CD19 chimeric antigen receptor (CAR) T-cells in adults with B-cell lymphoma. From October 2015 to October 2021, we treated five patients with B-cell lymphoma, comprising two with mantle cell lymphoma, one case of Burkitt lymphoma, one case of diffuse large B-cell lymphoma, and one case of chronic lymphocytic leukemia/small lymphocytic lymphoma. The patients were given the FC regimen 5 days before the infusion of anti-CD19 CAR T-cells. The median total number of CAR T-cells infusions was 35010^6 (8810^6-585*10^6). 1) Patients who received CAR T-cell induction therapy achieved complete remission (CR) in Case 1 and Case 3 and partial remission (PR) in Case 2. Case 3's ATM and D13S25 gene deletions were negative 42 days after CAR T-cell therapy, and molecular biology CR (mCR) and minimal residual disease (MRD) were negative for 5 years and 6 months. The patient in Case 3 was cured. 2) Case 4 patient's TP53 gene mutation became negative 1 month after CAR T-cell therapy. MRD was negative after CAR T-cell therapy at 41 and 42 months in Cases 4 and 5, respectively. 3) Case 1∼Case 3 patients developed cytokine release syndrome (CRS) without encephalopathy syndrome, accompanied with serious adverse events. CRS can be effectively managed with tocilizumab, etanercept, glucocorticoids, and plasmapheresis. Anti-CD19 CAR T-cell therapy is effective in treating relapsed/refractory B-cell lymphoma, and the side effects of CAR T-cell therapy can be properly managed. CAR T-cell therapy has high efficacy and presented no side effects in the treatment of MRD in B-cell lymphoma (NCT03685786, NCT02456350).
目的是研究抗CD19嵌合抗原受体（CAR）T细胞治疗成人B细胞淋巴瘤的益处和风险。2015年10月至2021年10月，我们治疗了5例B细胞淋巴瘤患者，其中包括2例套细胞淋巴瘤、1例伯基特淋巴瘤、1例弥漫性大B细胞淋巴瘤和1例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤。患者在输注抗CD19 CAR T细胞前5天接受FC方案治疗。CAR T细胞输注的中位数总数为350×10^6（88×10^6 - 585×10^6）。1）接受CAR T细胞诱导治疗的患者中，病例1和病例3达到完全缓解（CR），病例2达到部分缓解（PR）。病例3的ATM和D13S25基因缺失在CAR T细胞治疗后42天呈阴性，分子生物学CR（mCR）和微小残留病（MRD）在5年零6个月时均为阴性。病例3的患者被治愈。2）病例4患者的TP53基因突变在CAR T细胞治疗后1个月变为阴性。病例4和病例5的MRD分别在CAR T细胞治疗后41个月和42个月时为阴性。3）病例1至病例3的患者发生了细胞因子释放综合征（CRS），无脑病综合征，伴有严重不良事件。CRS可用托珠单抗、依那西普、糖皮质激素和血浆置换有效控制。抗CD19 CAR T细胞疗法在治疗复发/难治性B细胞淋巴瘤方面有效，且CAR T细胞疗法的副作用可得到妥善管理。CAR T细胞疗法在治疗B细胞淋巴瘤的MRD方面疗效高且无副作用（NCT03685786，NCT02456350）。
