Martino E A, Caridà G, Lofaro D, Bruzzese A, Labanca C, Mendicino F, Lucia E, Olivito V, Puccio N, Neri A, Amodio N, Vigna E, Morabito F, Gentile M
Hematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.
Hematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy; Department of Experimental and Clinical Medicine, University of Catanzaro, Catanzaro, Italy.
ESMO Open. 2025 Jul 15;10(8):105514. doi: 10.1016/j.esmoop.2025.105514.
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.
复发/难治性多发性骨髓瘤（RRMM）的治疗格局正在迅速演变，尤其是对于接受过来那度胺治疗或对其耐药的患者。为了评估不含来那度胺方案作为二线治疗选择的相对疗效，开展了一项纳入II/III期随机对照试验的更新网络荟萃分析。
系统文献检索确定了八项符合条件的试验，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论方法进行分析。
我们的研究结果表明，在首次复发时，贝兰他单抗马福多汀、硼替佐米和地塞米松（BVd）联合方案是对接受过来那度胺治疗和对来那度胺耐药的MM患者最有效的方案，在PFS的累积排名曲线下面积最高。BVd优于其他三联方案，包括达雷妥尤单抗、硼替佐米和地塞米松，isatuximab、卡非佐米和地塞米松，以及硼替佐米、泊马度胺和地塞米松。
包括嵌合抗原受体T细胞（CAR-T细胞）疗法和双特异性抗体在内的新兴疗法将重塑RRMM的治疗模式。CARTITUDE-4和MajesTEC-3等试验正在早期治疗线中探索这些药物，特别是对于对来那度胺和达雷妥尤单抗耐药的患者。我们的分析提供了一个基于证据的不含来那度胺方案的等级排序，支持BVd作为首选二线治疗方案。未来的研究应优化治疗顺序策略，并在疾病早期阶段评估新型药物，以优化RRMM患者的治疗结局。
