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来那度胺暴露或难治性多发性骨髓瘤患者随机对照试验的网络荟萃分析

英文原题:A network meta-analysis of randomized clinical trials in lenalidomide-exposed or -refractory multiple myeloma patients.

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A network meta-analysis of randomized clinical trials in lenalidomide-exposed or -refractory multiple myeloma patients.

PubMed 2025/07/15(内容时间) ESMO Open Q1 · IF 10.6(JCR 2025)

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研究概要

新兴疗法,包括 CAR-T 细胞(CAR-T 细胞)疗法和双特异性抗体,将重塑 RRMM 的治疗格局。诸如 CARTITUDE-4 和 MajesTEC-3 等试验正在探索这些药物在更早治疗线中的应用,特别是针对 lenalidomide 和 daratumumab 难治性患者。我们的分析提供了基于证据的无 lenalidomide 方案层级,支持 BVd 作为首选二线治疗。未来研究应完善治疗排序策略,并在更早疾病阶段评估新型药物,以优化 RRMM 患者的结局。

研究思路结论见上方概要

复发/难治性多发性骨髓瘤(RRMM)的治疗格局正在迅速演变,尤其是对于暴露于或对来那度胺难治的患者。为评估不含来那度胺的方案作为二线治疗选择的相对疗效,已开展了一项更新的网络 meta 分析,纳入了 II/III 期随机对照试验。

系统性文献检索确定了8项符合条件的试验,共纳入3952例患者。主要结局为无进展生存期(PFS),通过贝叶斯方法和频率学派方法进行分析。

我们的研究结果表明,belantamab mafodotin、bortezomib 和 dexamethasone(BVd)联合方案是 lenalidomide 暴露和 lenalidomide 难治性 MM 患者首次复发时最有效的方案,其 PFS 的累积排名曲线下面积最高。BVd 优于其他三联方案,包括 daratumumab、bortezomib 和 dexamethasone,isatuximab、carfilzomib 和 dexamethasone,以及 bortezomib、pomalidomide 和 dexamethasone。

展开英文摘要原文

The treatment landscape for relapsed/refractory multiple myeloma (RRMM) is rapidly evolving, particularly for patients exposed or refractory to lenalidomide. With the aim of evaluating the relative efficacy of lenalidomide-free regimens as second-line treatment options, an updated network meta-analysis, incorporating phase II/III randomized controlled trials, has been conducted.

A systematic literature search identified eight eligible trials comprising 3952 patients. The primary outcome was progression-free survival (PFS), analyzed through Bayesian and frequentist approaches.

Our findings indicate that belantamab mafodotin, bortezomib, and dexamethasone (BVd) combination is the most effective regimen for both lenalidomide-exposed and lenalidomide-refractory MM patients at first relapse, achieving the highest surface under the cumulative ranking curve for PFS. BVd outperformed other triplet regimens, including daratumumab, bortezomib, and dexamethasone, isatuximab, carfilzomib, and dexamethasone, and bortezomib, pomalidomide, and dexamethasone.

Emerging therapies, including chimeric antigen receptor T-cell (CAR-T-cell) therapy and bispecific antibodies, are set to reshape RRMM treatment paradigms. Trials such as CARTITUDE-4 and MajesTEC-3 are exploring these agents in earlier treatment lines, particularly for lenalidomide- and daratumumab-refractory patients. Our analysis provides an evidence-based hierarchy of lenalidomide-free regimens, supporting BVd as a preferred second-line treatment. Future studies should refine treatment sequencing strategies and evaluate novel agents in earlier disease stages to optimize outcomes for RRMM patients.

论文信息

作者
Martino EA、Caridà G、Lofaro D、Bruzzese A、Labanca C、Mendicino F、Lucia E、Olivito V
第一作者单位
Hematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.Italy
通讯作者单位
Hematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy; Department of Pharmacy, Health and Nutritional Science, University of Calabria, Rende, Italy. Electronic address: massimo.gentile@unical.it.Italy
文献类型
网状荟萃分析 · 系统综述
期刊
ESMO open2025 Aug
原文标识
PubMed 40669094 · DOI 10.1016/j.esmoop.2025.105514