对于难治性/复发性急性B细胞淋巴细胞白血病，单靶（CD19）CAR T细胞疗法和双靶（串联或顺序CD19/CD22）CAR T细胞疗法哪种更好？
Which one is better for refractory/relapsed acute B-cell lymphoblastic leukemia: Single-target (CD19) or dual-target (tandem or sequential CD19/CD22) CAR T-cell therapy?
发表日期：2023 Apr 24
作者：
Sining Liu, Xinyue Zhang, Haiping Dai, Wei Cui, Jia Yin, Zheng Li, Xiao Yang, Chunxiu Yang, Shengli Xue, Huiying Qiu, Miao Miao, Suning Chen, Zhengming Jin, Chengcheng Fu, Caixia Li, Aining Sun, Yue Han, Ying Wang, Lei Yu, Depei Wu, Qingya Cui, Xiaowen Tang
来源：
Blood Cancer Journal
摘要：
CD19嵌合抗原受体（CAR）T细胞疗法在B细胞急性淋巴细胞白血病（B-ALL）的治疗中显示出巨大成功。开发了串联和依次靶向CD19 / CD22双重靶向CAR T细胞疗法，以减少CD19阴性复发的可能性；然而，优越的策略仍不确定。本研究筛选了219名复发 / 难治性B-ALL患者，他们参加了CD19（NCT03919240）或CD19 / CD22 CAR T细胞治疗（NCT03614858）的临床试验。单一CD19，串联CD19 / CD22和依次CD19 / CD22组的完全缓解（CR）率分别为83.0％（122/147），98.0％（50/51）和95.2％（20/21）（单一CD19与串联CD19 / CD22比，P =0.006）。具有高危因素的患者在串联CD19 / CD22组中的CR率比单一CD19组更高（100.0％与82.4％，P =0.017）。串联CD19 / CD22 CAR T细胞疗法是CR率的多元分析中的重要有利因素之一。三组之间不良事件的发生率类似。CR患者的多元分析表明，低复发率、低肿瘤负荷、小残留病阴性CR和移植支架与更好的无白血病生存率独立相关。我们的研究结果表明，串联CD19 / CD22 CAR T细胞疗法获得了比CD19 CAR T细胞疗法更好的反应，并且与依次CD19 / CD22 CAR T细胞疗法有类似的反应。©2023. 作者。
CD19 chimeric antigen receptor (CAR) T-cell therapy has shown great success against B-cell acute lymphoblastic leukemia (B-ALL). Tandem and sequential CD19/CD22 dual-target CAR T-cell therapies have been developed to reduce the possibility of CD19-negative relapse; however, the superior strategy is still uncertain. This study screened 219 patients with relapsed/refractory B-ALL who were enrolled in clinical trials of either CD19 (NCT03919240) or CD19/CD22 CAR T-cell therapy (NCT03614858). The complete remission (CR) rates in the single CD19, tandem CD19/CD22, and sequential CD19/CD22 groups were 83.0% (122/147), 98.0% (50/51), and 95.2% (20/21), respectively (single CD19 vs. tandem CD19/CD22, P = 0.006). Patients with high-risk factors achieved a higher rate of CR in the tandem CD19/CD22 group than in the single CD19 group (100.0% vs. 82.4%, P = 0.017). Tandem CD19/CD22 CAR T-cell therapy was one of the significant favorable factors in the multivariate analysis of the CR rate. The incidence of adverse events was similar among the three groups. Multivariable analysis in CR patients showed that a low frequency of relapse, a low tumor burden, minimal residual disease-negative CR and bridging to transplantation were independently associated with better leukemia-free survival. Our findings suggested that tandem CD19/CD22 CAR T-cell therapy obtains a better response than CD19 CAR T-cell therapy and a similar response to sequential CD19/CD22 CAR T-cell therapy.© 2023. The Author(s).