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多发性骨髓瘤中的 CAR-T 细胞与双特异性抗体治疗:迈向未来

英文原题:Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapy in Multiple Myeloma: Moving Into the Future.

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Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapy in Multiple Myeloma: Moving Into the Future.

PubMed 2023/07/20(内容时间) J Clin Oncol Q1 · IF 44.7(JCR 2025)

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中文摘要

历史上,由于缺乏有效的治疗选择,三药耐药和五药耐药多发性骨髓瘤(MM)患者的结局一直很差。然而,嵌合抗原受体(CAR)T细胞和T细胞重定向双特异性抗体(BsAb)疗法的出现,在重度复发/难治(R/R)人群中带来了前所未有的缓解率和缓解持续时间。目前,美国已批准两种靶向B细胞成熟抗原(BCMA)的CAR-T 细胞疗法(idecabtagene vicleucel和ciltacabtagene autoleucel)以及一种BCMA/CD3 BsAb(teclistamab)用于晚期(既往超过四线治疗)R/R MM。本综述的目的是分析这些已获批疗法的最新数据,并概述其他正在开发的相关CAR-T 细胞和BsAb疗法,包括非BCMA靶向药物。

我们回顾了疗效和安全性方面的考量,特别关注细胞因子释放综合征、神经毒性和感染风险。讨论了每类疗法的相对优势和局限性,以及在最佳序贯治疗和支持治疗措施方面尚未满足的需求。

我们审视了在少数种族、族裔和社会经济人群中公平获得这些新疗法所面临的挑战因素。尽管显而易见,CAR-T 细胞和BsAb疗法将在未来数年改变MM的治疗范式,但仍有大量工作要做,以确定这些新疗法的最佳使用方式并确保公平可及。

展开英文摘要原文

Historically, the outcomes for individuals with triple-class refractory and penta-drug refractory multiple myeloma (MM) have been poor because of a dearth of effective treatment options.

However, the advent of chimeric antigen receptor (CAR) T-cell and T-cell redirecting bispecific antibody (BsAb) therapies has led to unprecedented response rates and durations of response in heavily relapsed/refractory (R/R) populations.

Currently, two B-cell maturation antigen (BCMA)-directed CAR T-cell therapies (idecabtagene vicleucel and ciltacabtagene autoleucel) as well as one BCMA/CD3 BsAb (teclistamab) have been approved for late-line (greater than four previous lines) R/R MM in the United States. The purpose of this review is to analyze the recent data for these approved therapies as well as provide an overview of other related CAR T-cell and BsAb therapies under development, including non-BCMA-targeting agents.

We review efficacy and safety considerations, with particular focus on cytokine release syndrome, neurotoxicity, and infection risk. The relative merits and limitations of each class of therapy are discussed, as well as the areas of unmet need with respect to optimal sequencing and supportive care measures.

We examine the factors that challenge equitable access to these novel therapies across minoritized racial, ethnic, and socioeconomic populations. Although it is evident that CAR T-cell and BsAb therapies will transform treatment paradigms in MM for years to come, significant work remains to identify the optimal utilization of these novel therapies and ensure equitable access.

论文信息

作者
Holstein SA、Grant SJ、Wildes TM
单位
Division of Oncology and Hematology, University of Nebraska Medical Center, Omaha, NE.
文献类型
综述 · 美国 NIH 资助研究
期刊
Journal of clinical oncology : official journal of the American Society of Clinical Oncology2023 Sep 20
原文标识
PubMed 37471687 · DOI 10.1200/JCO.23.00512