Data Sheet 1_Efficacy, safety and cost-effectiveness of obinutuzumab in patients with follicular lymphoma: a rapid review.docx

BackgroundObinutuzumab was approved in China in June 2021 used in combination with chemotherapy (followed by obinutuzumab maintenance) for the treatment of adult patients with previously untreated stage II bulky, III, or IV follicular lymphoma (FL). The clinical application of obinutuzumab has recently begun in China, but there is a lack of evidence to determine under which circumstances it should be considered the treatment of choice. A comprehensive assessment is necessary to evaluate the efficacy, safety, and cost-effectiveness of obinutuzumab in adult patients with FL.
ObjectiveTo summarize the evidence on the efficacy, safety, and cost-effectiveness of obinutuzumab in adult patients with FL, aiming to provide medical professionals with evidence for informed choices in clinical practice.
MethodsThe approach to this evidence synthesis was a rapid review of systematic reviews/meta-analyses (SR/meta-analyses), health technology assessment (HTA) reports, and pharmacoeconomic studies that brings together and summarizes the efficacy, safety, and cost-effectiveness of obinutuzumab in adult patients with FL. A literature search was conducted across multiple databases, including PubMed, Embase, Wanfang, CNKI, Weipu database, the Cochrane Library, the Centre for Reviews and Dissemination (CRD) database, International Network of Agencies for Health Technology Assessment (INAHTA) and Canada’s Drug Agency (CDA-AMC), International Society for Pharmacoeconomics and Outcomes Research (ISPOR), National Institute For Health and Care Excellence (NICE), Institute For Clinical And Economic Review (ICER), Grey Literature Database and Grey Net International. The studies on obinutuzumab for FL were searched in full text with obinutuzumab, systematic review, meta-analysis, economics, cost, and health technology assessment as keywords, with a search time frame from the date of database creation to 29 November 2024. The literature was screened based on predefined inclusion and exclusion criteria, and data were meticulously extracted and synthesized by two authors. Simultaneously, the quality of the literature was thoroughly assessed.
ResultsObinutuzumab based chemotherapy (the chemotherapy regimen-cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); cyclophosphamide, vincristine, and prednisone (CVP); or bendamustine) significantly prolonged progression free survival (PFS) compared to other chemotherapy regimen at primary and updated analyses. The incidence of grade 3–5 AEs, infusion-related reactions (IRRs), and infection were higher in the obinutuzumab based chemotherapy group compared to other chemotherapies. The economic researches conducted in China, United States, Japan, Italy and Norway had demonstrated that obinutuzumab-based chemothrepy was cost-effective compared to other chemothrepies. Although obinutuzumab significantly prolonged PFS and was cost-effective, its safety profile was considered lower.
ConclusionCompared with other chemothrapy regimen, obinutuzumab based chemotherapy significantly prolonged PFS and was cost-effective, while its safety profile was considered lower. Therefore, medical professionals should be caution when using or introducing obinutuzumab treatment for FL patients.

背景：奥妥珠单抗（Obinutuzumab）于2021年6月在华获批，联合化疗（后续予以奥妥珠单抗维持治疗）用于治疗既往未接受治疗的II期大肿块型、III期或IV期滤泡性淋巴瘤（Follicular Lymphoma, FL）成人患者。目前奥妥珠单抗在我国的临床应用刚起步，但尚缺乏明确证据以界定其适宜作为首选治疗方案的临床场景，亟需开展全面评估以明确奥妥珠单抗在FL成人患者中的疗效、安全性与成本效益。
目的：系统总结奥妥珠单抗用于FL成人患者的疗效、安全性及成本效益相关证据，为临床医护人员制定个体化诊疗决策提供循证依据。
方法：本证据综合研究采用快速回顾的方法，对系统评价/meta分析（Systematic Review/Meta-Analysis, SR/Meta-Analysis）、卫生技术评估（Health Technology Assessment, HTA）报告以及药物经济学研究进行检索整合，以汇总并阐明奥妥珠单抗用于FL成人患者的疗效、安全性与成本效益。检索覆盖多数据库，包括PubMed、Embase、万方数据库、中国知网（CNKI）、维普资讯网、Cochrane图书馆、循证医学中心（Centre for Reviews and Dissemination, CRD）数据库、国际卫生技术评估机构网络（International Network of Agencies for Health Technology Assessment, INAHTA）、加拿大药品署（Canada’s Drug Agency, CDA-AMC）、国际药物经济学与结果研究学会（International Society for Pharmacoeconomics and Outcomes Research, ISPOR）、英国国家卫生与临床优化研究所（National Institute For Health and Care Excellence, NICE）、美国临床与经济评价研究所（Institute For Clinical And Economic Review, ICER）、灰色文献数据库以及国际灰色文献网（Grey Net International）。以奥妥珠单抗、系统评价、meta分析、药物经济学、成本、卫生技术评估为关键词，对奥妥珠单抗治疗FL的相关研究进行全文检索，检索时限为各数据库建库起至2024年11月29日。按照预设的纳入与排除标准筛选文献，由两名研究者独立完成数据提取与整合，并对文献质量开展全面评估。
结果：在初始分析与更新分析中，以奥妥珠单抗为基础的化疗方案（联合环磷酰胺、多柔比星、长春新碱、泼尼松（CHOP）；环磷酰胺、长春新碱、泼尼松（CVP）；或苯达莫司汀）相较其他化疗方案，可显著延长患者的无进展生存期（Progression Free Survival, PFS）。奥妥珠单抗联合化疗组的3~5级不良事件（Adverse Events, AEs）、输液相关反应（Infusion-Related Reactions, IRRs）以及感染的发生率均高于其他化疗组。针对中国、美国、日本、意大利及挪威开展的药物经济学研究显示，以奥妥珠单抗为基础的化疗方案相较其他化疗方案具有成本效益优势。尽管奥妥珠单抗可显著延长PFS且具备成本效益，但其安全性表现相对欠佳。
结论：相较于其他化疗方案，以奥妥珠单抗为基础的化疗方案可显著延长FL患者的无进展生存期且具备成本效益，但安全性表现相对不足。因此，临床医护人员在为FL患者选用或引入奥妥珠单抗治疗方案时应谨慎权衡。