CD19-CART治疗复发难治性B细胞非霍奇金淋巴瘤的有效性及安全性

目的：探讨CD19-嵌合抗原受体T细胞（CART）治疗复发难治性B细胞非霍奇金淋巴瘤（B-NHL）的有效性及安全性。方法：评估2017年4月至2018年10月接受CD19-CART治疗的10例B-NHL患者的近期、远期随访疗效及不良反应。结果：10例患者均为复发、难治性淋巴瘤。10例患者输注CD19-CART后，总完全缓解（CR）率为30%，部分缓解（PR）率为40%，总有效率为70%。全部患者外周血中均检测到CD19-CART细胞的体内增殖，持续约3个月后快速下降。中位随访时间为9（1～24）个月。所有患者中位生存期（OS）为（10.5±4.0）个月，中位无进展生存期（PFS）为（4.6±3.9）个月。共8例患者输注CART后发生不同程度的细胞因子释放综合征（CRS），其中5例为1级CRS，2例为2级CRS，仅1例发生4级CRS及神经毒性。2例使用IL-6受体单克隆抗体-托珠单抗，其中1例联合使用糖皮质激素。除1例4级CRS患者输注后第18天因神经毒性死亡外，其余患者CRS均得到有效控制。结论：针对B-NHL的CD19-CART疗法取得了一定的疗效，其可作为复发难治患者的挽救治疗，且不良反应可控。及时地监测及管理输注期的不良反应有助于防止不可控结局的发生。

Efficacy and safety of CD19-CART in the treatment of relapsed refractory non-Hodgkin’s B-cell lymphoma

Objective: To investigate the therapeutic efficacy and safety of CD19 chimeric antigen receptor T cells (CART) for the relapsed/refractory B-cell non-Hodgkin’s lymphoma (B-NHL). Methods: After close follow-up, the short-term and long-term response and adverse effect (AEs) of 10 patients with B-NHL who received CD19-CART therapy from April 2017 to October 2018 were evaluated. Results: All patients were with relapsed/refractory lymphoma. After infusion of CD19-CART cells in 10 patients, the total complete response (CR) rate was 30%, the partial response (PR) rate was 40%, and the overall response rate was 70%. In vivo proliferation of CD19-CART cells was detected in peripheral blood of all patients, which decreased rapidly after about 3 months. The median follow-up was 9 (1-24) months. The median overall survival (OS) of all patients was (10.5±4.0) months, and the median progression-free survival (PFS) was (4.6±3.9) months. A total of 8 patients (8/10) had cytokine release syndrome (CRS) after infusion of CART cells, of which five were grade 1 CRS, two were grade 2 CRS and one was grade 4 CRS accompanying with grade 4 neurotoxicity. Two patients used Tocilizumab (IL-6 receptor monoclonal antibody), and one patient was treated combined with glucocorticoids. Except for one patient suffering from grade 4 CRS who died of grade 4 neurotoxicity on the 18th day after infusion, the other patients with CRS were effectively controlled. Conclusion: Since CART therapy for relapsed/refractory CD19+ B cell lymphoma has achieved certain effect in some ways and the AEs were controllable, it could be used as a salvage treatment for relapsed/refractory patients. Timely monitoring and management of AEs during the infusion period might help prevent the uncontrollable outcomes.