双唾液酸神经节苷脂靶向疗法治疗儿童神经母细胞瘤安全性的系统评价和Meta分析  

Safety of disialoganglioside targeted therapies in the treatment of pediatric neuroblastoma:a systematic review and Meta-analysis

作　　者：邢颖 逄瑜 詹思延[1] XING Ying;PANG Yu;ZHAN Siyan(Department of Epidemiology and Biostatistics,School of Public Health,Peking University,Beijing 100191,China;Tonghua Anrate Biopharmaceutical Co.,Ltd.,Beijing 100071,China)

机构地区：[1]北京大学公共卫生学院流行病与卫生统计学系,北京100191 [2]通化安睿特生物制药股份有限公司,北京100071

出　　处：《药物流行病学杂志》2025年第2期191-204,共14页Chinese Journal of Pharmacoepidemiology

摘　　要：目的系统评价双唾液酸神经节苷脂(GD2)靶向疗法治疗儿童神经母细胞瘤(NB)的安全性。方法计算机检索PubMed、Embase、Cochrane Library、CNKI、WanFang Data、SinoMed数据库及ClinicalTrials.gov临床试验注册平台,搜集有关GD2靶向疗法治疗儿童NB的临床研究,检索时限均从建库至2024年11月30日。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用R软件4.3.1进行Meta分析。结果共纳入21项研究,包括2438例患儿。Meta分析结果显示,NB患儿接受GD2靶向疗法治疗后,严重药品不良事件(SADE)总体发生率及其95%置信区间(CI)为51.67%(35.43%、67.92%),其中严重发热和丙氨酸转氨酶升高较常见,发生率及其95%CI分别为7.80%(0.80%、18.85%)、5.10%(2.02%、10.55%)。3~5级药品不良反应(ADR)发生率及其95%CI:发热18.81%(8.00%、29.61%)、疼痛30.32%(16.21%、44.44%)、低钾血症18.96%(6.44%、31.49%)、丙氨酸转氨酶升高10.41%(2.96%、17.86%)、低血压8.48%(3.78%、13.18%)、贫血16.62%(5.97%、27.26%)、血小板减少16.46%(5.55%、27.37%)、淋巴细胞减少10.42%(0.97%、26.09%)、中性粒细胞减少13.37%(3.12%、23.62%)。在各干预措施亚组中,达妥昔单抗β组和GD2特异性嵌合抗原受体T细胞(GD2 CART)疗法组3~5级ADR发生率相对较低。结论NB患儿接受GD2靶向疗法治疗后,SADE及3~5级ADR发生率较高,应予以重视。在研的GD2靶向疗法治疗儿童NB的安全性特征不逊于甚至更优于已上市GD2靶向药物,特别是GD2 CART疗法展现出良好的安全性潜力。Objective To systematically review the safety of disialoganglioside(GD2)targeted therapies in the treatment of pediatric neuroblastoma(NB).Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data,SinoMed databases and ClinicalTrials.gov clinical trial registration system were electronically searched to collect clinical studies of GD2-targeted therapies for pediatric NB from inception to November 30,2024.Two reviewers independently screened the literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was performed by using R 4.3.1 software.Results A total of 21 studies involving 2,438 patients were included.Meta-analysis results showed that the overall incidence(95%CI)of serious adverse drug events(SADEs)in GD2-targeted therapies for pediatric NB was 51.67%(35.43%to 67.92%).The serious fever and alanine aminotransferase(ALT)increase were common with the incidence(95%CI)of 7.80%(0.80%to 18.85%)and 5.10%(2.02%to 10.55%)respectively.The incidences(95%CI)of grade 3 to 5 adverse drug reactions(ADRs):fever 18.81%(8.00%to 29.61%),pain 30.32%(16.21%to 44.44%),hypokalemia 18.96%(6.44%to 31.49%),ALT increased 10.41%(2.96%to 17.86%),hypotension 8.48%(3.78%to 13.18%),anemia 16.62%(5.97%to 27.26%),platelet count decreased 16.46%(5.55%to 27.37%),lymphocyte count decreased 10.42%(0.97%to 26.09%),neutrophil count decreased 13.37%(3.12%to 23.62%).Among the intervention subgroups,the incidences of grade 3 to 5 ADRs were relatively low in dinutuximabβgroup and GD2-chimeric antigen receptor T cells(GD2 CART)group.Conclusions The incidences of SADEs and grade 3 to 5 ADRs are high in pediatric NB patients receiving GD2-targeted therapy,which should be paid attention to.The safety profile of GD2 targeted therapies under development for pediatric NB are even better than those of GD2 targeted drugs already on the market,especially GD2 CART,which shows good safety potential.

关 键 词：双唾液酸神经节苷脂 神经母细胞瘤 安全性 系统评价 META分析 

分 类 号：R739.4[医药卫生—肿瘤] R969.3[医药卫生—临床医学]