Ntsethe Aviwe, Dludla Phiwayinkosi Vusi, Nyambuya Tawanda Maurice, Ngcobo Siphamandla Raphael, Nkambule Bongani Brian
School of Laboratory Medicine and Medical Sciences (SLMMS), College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.
Medicine (Baltimore). 2020 Jul 10;99(28):e21167. doi: 10.1097/MD.0000000000021167.
The global burden of chronic lymphocytic leukemia (CLL) has constantly increased over the years, with a current incidence of 3.5 cases per 100,000 people. Although the conventional drugs used to treat CLL patients have been effective treatment failure rate in some of the patients is alarming. Therefore, as a result, novel treatment strategies with improved outcomes such as the blockade of immune checkpoints have emerged. However, consensus on the risk-benefit effects of the using these drugs in patients with CLL is controversial and has not been comprehensively evaluated. This systemic review and meta-analysis provide a comprehensive synthesis of available data assessing adverse events associated with the use of immune checkpoint inhibitors in patients with CLL as well as their influence on the overall survival rate.
This protocol for a systematic review and meta-analysis has been prepared in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines. A search strategy will be developed using medical subject headings words in PubMed search engine with MEDLINE database. The search terms will also be adapted for gray literature, Embase, and Cochrane Central Register of Controlled Trials electronic databases. Two reviewers (AN and SRN) will independently screen studies, with a third reviewer consulted in cases of disagreements using a defined inclusion and exclusion criteria. Data items will be extracted using a predefined data extraction sheet. Moreover, the risk of bias and quality of the included studies will be appraised using the Downs and Black checklist and the quality and strengths of evidence across selected studies will be assessed using the Grading of Recommendations Assessment Development and Evaluation approach. The Cochran's Q statistic and the I statistics will be used to analyze statistical heterogeneity across studies. If the included studies show substantial level of statistical heterogeneity (I > 50%), a random-effects meta-analysis will be performed using R statistical software.
The review and meta-analysis will not require ethical approval and the findings will be published in peer-reviewed journals and presented at local and international conferences. This review may help provide clarity on the risk-benefit effects of using immune checkpoint inhibitors in patients with CLL.
International prospective Register of Systematic Reviews (PROSERO) number: CRD42020156926.
多年来，慢性淋巴细胞白血病（CLL）的全球负担持续增加，目前发病率为每10万人中有3.5例。尽管用于治疗CLL患者的传统药物一直有效，但部分患者的治疗失败率令人担忧。因此，诸如免疫检查点阻断等具有更好疗效的新型治疗策略应运而生。然而，关于在CLL患者中使用这些药物的风险效益影响的共识存在争议，且尚未得到全面评估。本系统评价和荟萃分析全面综合了现有数据，评估了CLL患者使用免疫检查点抑制剂相关的不良事件及其对总生存率的影响。
本系统评价和荟萃分析方案已按照《系统评价和荟萃分析方案的首选报告项目2015指南》编制。将使用PubMed搜索引擎中的医学主题词与MEDLINE数据库制定检索策略。检索词也将适用于灰色文献、Embase和Cochrane对照试验中央注册库电子数据库。两名评审员（AN和SRN）将独立筛选研究，如有分歧将由第三名评审员根据既定的纳入和排除标准进行协商。将使用预定义的数据提取表提取数据项。此外，将使用唐斯和布莱克清单评估纳入研究的偏倚风险和质量，并使用推荐分级评估、制定和评价方法评估所选研究的证据质量和强度。将使用 Cochr an's Q统计量和I统计量分析各研究之间的统计异质性。如果纳入研究显示出较高水平的统计异质性（I>50%），将使用R统计软件进行随机效应荟萃分析。
本评价和荟萃分析无需伦理批准，研究结果将发表在同行评审期刊上，并在地方和国际会议上展示。本评价可能有助于明确在CLL患者中使用免疫检查点抑制剂的风险效益影响。
国际前瞻性系统评价注册库（PROSERO）编号：CRD42020156926。
