嵌合抗原受体（CAR）T 细胞治疗 B 细胞恶性肿瘤患者的疗效和安全性的系统评价和荟萃分析方案。
Efficacy and safety of CD22 chimeric antigen receptor (CAR) T cell therapy in patients with B cell malignancies: a protocol for a systematic review and meta-analysis.
机构信息
Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
出版信息
Syst Rev. 2021 Jan 21;10(1):35. doi: 10.1186/s13643-021-01588-7.
BACKGROUND
Chimeric antigen receptor (CAR) T cell therapy has had great success in treating patients with relapsed or refractory B cell malignancies, with CD19-targeting therapies now approved in many countries. However, a subset of patients fails to respond or relapse after CD19 CAR T cell therapy, in part due to antigen loss, which has prompted the search for alternative antigen targets. CD22 is another antigen found on the surface of B cells. CARs targeting CD22 alone or in combination with other antigens have been investigated in several pre-clinical and clinical trials. Given the heterogeneity and small size of CAR T cell therapy clinical trials, systematic reviews are needed to evaluate their efficacy and safety. Here, we propose a systematic review of CAR T cell therapies targeting CD22, alone or in combination with other antigen targets, in B cell malignancies.
METHODS
We will perform a systematic search of EMBASE, MEDLINE, Web of Science, Cochrane Register of Controlled Trials, clinicaltrials.gov, and the International Clinical Trials Registry Platform. Ongoing and completed clinical trials will be identified and cataloged. Interventional studies investigating CD22 CAR T cells, including various multi-antigen targeting approaches, in patients with relapsed or refractory B cell malignancies will be eligible for inclusion. Only full-text articles, conference abstracts, letters, and case reports will be considered. Our primary outcome will be a complete response, defined as absence of detectable cancer. Secondary outcomes will include adverse events, overall response, minimal residual disease, and relapse, among others. Quality assessment will be performed using a modified Institute of Health Economics tool designed for interventional single-arm studies. We will report a narrative synthesis of clinical studies, presented in tabular format. If appropriate, a meta-analysis will be performed using a random effects model to synthesize results.
DISCUSSION
The results of the proposed review will help inform clinicians, patients, and other stakeholders of the risks and benefits of CD22 CAR T cell therapies. It will identify gaps or inconsistencies in outcome reporting and help to guide future clinical trials investigating CAR T cells.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration number: CRD42020193027.
背景
嵌合抗原受体 (CAR) T 细胞疗法在治疗复发或难治性 B 细胞恶性肿瘤患者方面取得了巨大成功，许多国家现已批准针对 CD19 的靶向治疗药物。然而，一部分患者在接受 CD19 CAR T 细胞治疗后无法响应或复发，部分原因是抗原丢失，这促使人们寻找替代的抗原靶标。CD22 是 B 细胞表面的另一种抗原。针对 CD22 的 CAR 单独或与其他抗原联合已在几项临床前和临床试验中进行了研究。鉴于 CAR T 细胞治疗临床试验的异质性和规模较小，需要进行系统评价来评估其疗效和安全性。在这里，我们提出了一项针对 CD22 的 CAR T 细胞疗法的系统评价，单独或与其他抗原靶标联合用于 B 细胞恶性肿瘤。
方法
我们将对 EMBASE、MEDLINE、Web of Science、Cochrane 对照试验登记处、clinicaltrials.gov 和国际临床试验注册平台进行系统搜索。将确定和编目正在进行和已完成的临床试验。将纳入研究复发或难治性 B 细胞恶性肿瘤患者中 CD22 CAR T 细胞的干预性研究，包括各种多抗原靶向方法。仅考虑全文文章、会议摘要、信件和病例报告。我们的主要结局将是完全缓解，定义为无癌可检测。次要结局将包括不良事件、总反应、微小残留病和复发等。使用专为干预性单臂研究设计的改良卫生经济研究所工具进行质量评估。我们将以表格形式报告临床研究的叙述性综合，如有必要，将使用随机效应模型进行荟萃分析以综合结果。
讨论
该综述的结果将有助于向临床医生、患者和其他利益相关者告知 CD22 CAR T 细胞疗法的风险和益处。它将确定结果报告中的差距或不一致之处，并有助于指导未来针对 CAR T 细胞的临床试验。
系统评价注册
PROSPERO 注册号：CRD42020193027。
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