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新型抗 CD20 单克隆抗体与利妥昔单抗用于 CD20 B 细胞非霍奇金淋巴瘤诱导治疗的疗效和安全性:系统评价和荟萃分析。

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20 B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis.

机构信息

Center for Hematology, Southwest Hospital, Third Military Medical University, Chongqing, China.

Key Laboratory of Cancer Immunotherapy of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.

出版信息

Sci Rep. 2021 Feb 5;11(1):3255. doi: 10.1038/s41598-021-82841-w.

Abstract

Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20 B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel-Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5261 patients with CD20 B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73-0.96, P = 0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95% CI 1.13-1.48, P < 0.001). Ofatumumab was inferior to rituximab in consideration of ORR (OR 0.73, 95% CI 0.55-0.96, P = 0.02), and had no significant differences with rituximab in regard to PFS, OS and CRR. I-tositumomab yielded similar PFS, OS, ORR and CRR with rituximab. Y-ibritumomab tiuxetan increased ORR (OR 3.07, 95% CI 1.47-6.43, P = 0.003), but did not improve PFS, DFS, OS and CRR compared with rituximab. In conclusion, compared with rituximab in induction therapy of CD20 B-NHL, obinutuzumab significantly improves PFS but with higher incidence of AEs, ofatumumab decreases ORR, Y-ibritumomab tiuxetan increases ORR.

摘要

奥滨尤妥珠单抗联合化疗是 CD20 阳性 B 细胞非霍奇金淋巴瘤(CD20 B-NHL)的一线诱导治疗方案。最近,新的抗 CD20 单克隆抗体(mAbs)已经被开发出来,但它们与利妥昔单抗相比的疗效和安全性仍存在争议。我们检索了 MEDLINE、Embase 和 Cochrane Library,以纳入比较新的抗 CD20 mAbs 与利妥昔单抗在 B-NHL 诱导治疗中的随机对照试验(RCTs)。主要结局是无进展生存期(PFS)和总生存期(OS),额外结局包括无事件生存期(EFS)、无疾病生存期(DFS)、总缓解率(ORR)、完全缓解率(CRR)和不良事件(AEs)发生率。使用固定效应模型汇总时间依赖性数据作为风险比(HRs),使用 Mantel-Haenszel 方法汇总二分类结局作为比值比(ORs),并分别给出其 95%置信区间(CI)。纳入了 11 项包含 5261 例 CD20 B-NHL 患者的 RCTs。与利妥昔单抗相比,奥滨尤妥珠单抗显著延长了 PFS(HR 0.84,95%CI 0.73-0.96,P=0.01),但对 OS、ORR 和 CRR 没有改善,反而增加了严重 AEs 的发生率(OR 1.29,95%CI 1.13-1.48,P<0.001)。奥法木单抗在考虑 ORR 时劣于利妥昔单抗(OR 0.73,95%CI 0.55-0.96,P=0.02),但在 PFS、OS 和 CRR 方面与利妥昔单抗没有显著差异。伊妥珠单抗与利妥昔单抗相比,PFS、OS、ORR 和 CRR 相似。替伊莫单抗替昔布与利妥昔单抗相比,增加了 ORR(OR 3.07,95%CI 1.47-6.43,P=0.003),但没有改善 PFS、DFS、OS 和 CRR。总之,与利妥昔单抗在 CD20 B-NHL 的诱导治疗相比,奥滨尤妥珠单抗显著改善了 PFS,但不良反应发生率更高,奥法木单抗降低了 ORR,替伊莫单抗替昔布增加了 ORR。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f20/7864901/8cb3320ee67c/41598_2021_82841_Fig1_HTML.jpg

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