Optimal daratumumab-based regimen for patients with newly diagnosed and previously untreated multiple myeloma: systematic review and component network meta-analysis.

IF 6.3 4区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Xiaohua Huang, Jia Zhou, Yuxiao Qian, Jing He, Lu Yang, Zhigang Wang, Diu Wei, Mengjie Li, Wei Ma, Haiyan Lang
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引用次数: 0

Abstract

Background: Daratumumab (Dara)-based regimens have been investigated in randomized controlled trials (RCTs) involving patients with newly diagnosed and previously untreated multiple myeloma (NDMM), but the optimal daratumumab-based regimen remains unclear. This study compares the efficacy of daratumumab-containing regimens for NDMM patients and explores optimal combinations.

Methods: Databases were searched from inception until February 29, 2024. Trials comparing regimens with and without daratumumab, as well as their mutual comparisons, were included. Random effects models for serious adverse events (SAEs) and fixed effects models for other outcomes were utilized in both network meta-analysis (NMA) and component NMA (CNMA), with pooled effects estimated. The efficacy of all possible combinations of daratumumab with other drugs was assessed.

Results: A total of 17 trials were included, enrolling 7261 patients, of whom 2083 were treated with daratumumab. The optimal regimens for different outcomes were identified as follows: Dara-bortezomib (V)-melphalan (M)-corticosteroids (D) (Dara-VMD) showed the best results for both overall response rate (ORR) [RR = 1.97; 95% CI: 1.42 to 2.75; I2 = 0.00%; 16 trials; 7136 participants; P = 0.00] and ≥ very good partial response (≥ VGPR) [RR = 7.46; 95% CI: 4.10 to 13.46; I2 = 23.96%; 16 trials; 7118 participants; P = 0.00]; Dara-V-thalidomide (T)-D (Dara-VTD) was optimal for achieving ≥ complete response (≥ CR) [RR = 14.15; 95% CI: 3.74 to 53.52; I2 = 0.00%; 17 trials; 7261 participants; P = 0.00]. The individual effects of daratumumab were calculated as follows: [ORR: RR = 1.14; 95% CI: 1.08 to 1.21; I2 = 0.00%; 16 trials; 7136 participants; P = 0.00; ≥ VGPR: RR = 1.46; 95% CI: 1.36 to 1.58; I2 = 23.96%; 16 trials; 7118 participants; P = 0.00; ≥ CR: RR = 1.77; 95% CI: 1.55 to 1.99; I2 = 0.00; 17 trials; 7261 participants; P = 0.00; progression-free survival (PFS): hazard ratio (HR) = 0.53; 95% CI: 0.43 to 0.65; I2 = 0.00%; 13 trials; 5977 participants; P = 0.00; overall survival (OS): HR = 0.68; 95% CI: 0.58 to 0.79; I2 = 28.97%; 12 trials; 5977 participants; P = 0.00]. Additionally, the optimal regimens for PFS and OS were Dara-lenalidomide (R)-D [HR = 0.37; 95% CI: 0.23 to 0.61; I2 = 0.00%; 13 trials; 5977 participants; P = 0.00] and Dara-VRD [HR = 0.40; 95% CI: 0.19 to 0.85; I2 = 28.97%; 12 trials; 5977 participants; P = 0.02], respectively. Finally, CNMA indicated that Dara-VRD, Dara-carfilzomib (K)-RD, Dara-RD, and Dara-cyclophosphamide (C)-RD were four regimens, which could improve remission rate, and reduce death or progression during induction and prolong lifetime.

Conclusions: Dara-VRD, Dara-KRD, Dara-RD, and Dara-CRD are optimal daratumumab-based regimens for patients with newly diagnosed and previously untreated multiple myeloma.

新诊断和未治疗的多发性骨髓瘤患者的最佳达拉图单抗方案:系统评价和成分网络荟萃分析
背景:基于Daratumumab (Dara)的方案已经在随机对照试验(RCTs)中进行了研究,涉及新诊断和先前未治疗的多发性骨髓瘤(NDMM)患者,但基于Daratumumab的最佳方案尚不清楚。本研究比较了含daratumumab方案对NDMM患者的疗效,并探索了最佳组合。方法:检索自成立至2024年2月29日的数据库。包括比较使用和不使用daratumumab方案的试验,以及它们之间的相互比较。在网络荟萃分析(NMA)和成分荟萃分析(CNMA)中,使用严重不良事件(sae)的随机效应模型和其他结果的固定效应模型,并估计汇总效应。评估了所有可能的daratumumab与其他药物联合使用的疗效。结果:共纳入17项试验,纳入7261例患者,其中2083例患者接受了daratumumab治疗。不同结果的最佳方案确定如下:达拉-硼替佐米(V)-美法兰(M)-皮质类固醇(D)(达拉- vmd)在总缓解率(ORR) [RR = 1.97;95% CI: 1.42 ~ 2.75;i2 = 0.00%;16试验;7136名参与者;P = 0.00]和≥极好部分反应(≥VGPR) [RR = 7.46;95% CI: 4.10 ~ 13.46;i2 = 23.96%;16试验;7118名参与者;p = 0.00];达拉- v -沙利度胺(T)-D(达拉- vtd)是达到≥完全缓解(≥CR)的最佳药物[RR = 14.15;95% CI: 3.74 ~ 53.52;i2 = 0.00%;17个试验;7261名参与者;p = 0.00]。daratumumab的个体效应计算如下:[ORR: RR = 1.14;95% CI: 1.08 ~ 1.21;i2 = 0.00%;16试验;7136名参与者;P = 0.00,≥vgpr: rr = 1.46;95% CI: 1.36 ~ 1.58;i2 = 23.96%;16试验;7118名参与者;P = 0.00,≥cr: rr = 1.77;95% CI: 1.55 ~ 1.99;i2 = 0.00;17个试验;7261名参与者;p = 0.00;无进展生存期(PFS):风险比(HR) = 0.53;95% CI: 0.43 ~ 0.65;i2 = 0.00%;13试验;5977名参与者;p = 0.00;总生存期(OS): HR = 0.68;95% CI: 0.58 ~ 0.79;i2 = 28.97%;12试验;5977名参与者;p = 0.00]。此外,PFS和OS的最佳方案是达拉-来那度胺(R)-D [HR = 0.37;95% CI: 0.23 ~ 0.61;i2 = 0.00%;13试验;5977名参与者;P = 0.00]和Dara-VRD [HR = 0.40;95% CI: 0.19 ~ 0.85;i2 = 28.97%;12试验;5977名参与者;P = 0.02]。最后,CNMA指出,达拉- vrd、达拉-卡非佐米(K)-RD、达拉-RD和达拉-环磷酰胺(C)-RD 4种方案可提高缓解率,减少诱导过程中的死亡或进展,延长生存期。结论:Dara-VRD、Dara-KRD、Dara-RD和Dara-CRD是新诊断和未治疗的多发性骨髓瘤患者的最佳方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Systematic Reviews
Systematic Reviews Medicine-Medicine (miscellaneous)
CiteScore
8.30
自引率
0.00%
发文量
241
审稿时长
11 weeks
期刊介绍: Systematic Reviews encompasses all aspects of the design, conduct and reporting of systematic reviews. The journal publishes high quality systematic review products including systematic review protocols, systematic reviews related to a very broad definition of health, rapid reviews, updates of already completed systematic reviews, and methods research related to the science of systematic reviews, such as decision modelling. At this time Systematic Reviews does not accept reviews of in vitro studies. The journal also aims to ensure that the results of all well-conducted systematic reviews are published, regardless of their outcome.
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