CD22 CAR T 细胞单独或与 CD19 CAR T 细胞联合应用的系统评价和荟萃分析。

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells.

机构信息

Department of Medicine, University of Toronto, Toronto, ON, Canada.

Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

出版信息

Front Immunol. 2023 Apr 27;14:1178403. doi: 10.3389/fimmu.2023.1178403. eCollection 2023.

UNLABELLED

Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/prospero, identifier CRD42020193027.

目的

评估 CD22 靶向嵌合抗原受体 (CAR) T 细胞疗法的疗效和安全性。

方法

我们检索了 MEDLINE、EMBASE、Web of Science 和 Cochrane 对照试验中心注册库，以获取截至 2022 年 3 月 3 日关于 CD22 靶向 CAR T 细胞治疗急性淋巴细胞白血病 (ALL) 和非霍奇金淋巴瘤 (NHL) 的临床试验的全文文章和会议摘要。主要结局指标是最佳完全缓解 (bCR)。采用 DerSimonian 和 Laird 随机效应模型进行 arcsine 变换以汇总结局比例。

结果

从筛选出的 1068 篇参考文献中，纳入了 100 篇研究，代表了 30 项早期研究，共有 637 例患者，研究了 CD22 或 CD19/CD22 CAR T 细胞。CD22 CAR T 细胞在 ALL（n=116）中的 bCR 为 68%（95%CI，53-81%），在 NHL（n=28）中的 bCR 为 64%（95%CI，46-81%），分别有 74%和 96%的患者在 ALL 和 NHL 研究中先前接受过抗 CD19 CAR T 细胞治疗。CD19/CD22 CAR T 细胞在 ALL（n=297）中的 bCR 率为 90%（95%CI，84-95%），在 NHL（n=137）中的 bCR 率为 47%（95%CI，34-61%）。总细胞因子释放综合征 (CRS) 和严重（等级≥3）CRS 的估计发生率分别为 87%（95%CI，80-92%）和 6%（95%CI，3-9%）。免疫细胞激活的神经毒性综合征 (ICANS) 和严重 ICANS 的估计发生率分别为 16%（95%CI，9-25%）和 3%（95%CI，1-5%）。