肿瘤细胞治疗研究
英文原题:Revolutionizing 2L+ Myeloma: A Podcast on the New Era of BCMA-Targeted Bispecific Antibody Therapies.
Revolutionizing 2L+ Myeloma: A Podcast on the New Era of BCMA-Targeted Bispecific Antibody Therapies.
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基于达雷妥尤单抗的三联和四联方案作为新诊断多发性骨髓瘤(MM)的一线(1L)治疗,已显著改善患者结局。然而,随着可用1L联合方案的演变,首次复发时对多种治疗类别暴露且难治的患者比例正在增加。患者随着每一次连续复发预后逐渐恶化,且随着每一线治疗(LOT),脱落率增加。
因此,在二线及以后(2L+)治疗中,关键在于尽早使用最有效的可用治疗以优化患者结局。靶向B细胞成熟抗原(BCMA)的治疗,尤其是CAR-T 细胞疗法,正迅速成为新的2L+标准治疗(SOC)。其他BCMA靶向选择,包括belantamab mafodotin联合地塞米松再加硼替佐米或泊马度胺,已在2L+治疗中显示出有前景的疗效。BCMA靶向双特异性抗体是一种正在更早LOT中探索的新治疗选择,为患者提供了一种减少类固醇使用的方案,并具有在所有实践环境中使用的潜力。基于3期MajesTEC-3试验的结果,teclistamab联合达雷妥尤单抗已在美国获批用于既往接受≥ 1线LOT的患者,该试验中teclistamab-daratumumab在既往接受1至3线LOT的患者中较SOC显著改善了无进展生存期和总生存期。
多项针对BCMA的双特异性抗体在更早LOT中的其他临床试验正在进行中,包括teclistamab单药治疗(MajesTEC-9)、teclistamab联合G蛋白偶联受体C类第5组成员D(GPRC5D)靶向双特异性抗体talquetamab(MonumenTAL-6)、elranatamab(MagnetisMM-5)和linvoseltamab(LINKER-MM3),为首次复发后患者治疗选择的下一步演变铺平了道路。在本播客中,2位领先的血液学家讨论了2L+ MM中未满足的需求、治疗决策的考量因素以及不断演变的治疗格局,重点关注BCMA靶向双特异性抗体——这一在该背景下快速进展的治疗类别。补充文件1(MP4 179036 KB)。
Daratumumab-based triplet and quadruplet regimens have significantly improved patient outcomes as first-line (1L) treatment in newly diagnosed multiple myeloma (MM).
However, with the evolution of available 1L combination regimens, the proportion of patients with exposure and refractoriness to multiple treatment classes at first relapse is increasing. Patients experience worsening prognosis with each successive relapse, and attrition rates increase with each line of therapy (LOT).
Therefore, in the second-line setting and beyond (2L+), it is critical to use the most effective treatment available up front to optimize patient outcomes. Treatments that target the B-cell maturation antigen (BCMA), particularly chimeric antigen receptor T-cell therapy, are rapidly becoming a new 2L+ standard of care (SOC). Other BCMA-targeted options, including combinations of belantamab mafodotin plus dexamethasone with bortezomib or pomalidomide, have shown promising efficacy in the 2L+ setting. BCMA-targeted bispecific antibodies are a new treatment option being explored in earlier LOTs and offer patients a steroid-sparing approach with the potential for use across all practice settings. Teclistamab combined with daratumumab is approved in the United States for patients with ≥ 1 prior LOT based on results of the phase 3 MajesTEC-3 trial, in which teclistamab-daratumumab significantly improved progression-free and overall survival versus SOC in patients with 1 to 3 prior LOTs.
Several other clinical trials of BCMA-targeted bispecific antibodies in earlier LOTs are ongoing, including teclistamab monotherapy (MajesTEC-9), teclistamab combined with the G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted bispecific antibody talquetamab (MonumenTAL-6), elranatamab (MagnetisMM-5), and linvoseltamab (LINKER-MM3), paving the way for the next evolution of treatment options for patients following first relapse.
In this podcast, 2 leading hematologists discuss the unmet needs in 2L+ MM, considerations for treatment decisions, and the evolving treatment landscape with a focus on BCMA-targeted bispecific antibodies, a rapidly advancing class of treatments in this setting. Supplementary file1 (MP4 179036 KB).
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