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快而猛:多发性骨髓瘤中 CAR-T 细胞治愈之路上的换挡

英文原题:Fast and furious: Changing gears on the road to cure with chimeric antigen receptor T cells in multiple myeloma.

查看英文原题

Fast and furious: Changing gears on the road to cure with chimeric antigen receptor T cells in multiple myeloma.

PubMed 2024/07/06(内容时间) Semin Hematol Q1 · IF 4.3(JCR 2025)

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中文摘要

基于关键的KarMMa-1和CARTITUDE-1研究,Idecabtagene vicleucel(Ide-cel)和Ciltacabtagene autoleucel(Cilta-cel)已获批用于治疗多发性骨髓瘤患者,这些患者分别在接受4线或3线治疗后,已暴露于至少1种蛋白酶体抑制剂、免疫调节药物和抗CD38抗体。与此同时,多项真实世界分析已证实了前所未有的深度且持久缓解率,而最近KarMMa-3和CARTITUDE-4研究促使了在更早期治疗线中的获批。目前认为,最终所有复发/难治性多发性骨髓瘤患者在抗BCMA CAR-T 细胞治疗后都会复发。针对新型抗原的大量CAR-T 细胞疗法旨在克服当前的CAR-T 细胞耐药性。在本综述中,我们将总结新型抗原的当前证据及其临床潜力。与当前的CAR-T 细胞疗法和T细胞衔接器一起,这些方法可能引领我们进入多发性骨髓瘤的下一个前沿:全免疫治疗和通往无化疗治愈的道路。

展开英文摘要原文

Based on the pivotal KarMMa-1 and CARTITUDE-1 studies, Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel) have been approved to treat multiple myeloma patients, who have been exposed to at least 1 proteasome inhibitor, immunomodulatory drug and anti-CD38 antibody after 4 or 3 lines of therapy, respectively. The unprecedented rates of deep and long-lasting remissions have been meanwhile confirmed in multiple real-world analyses and more recently, the KarMMa-3 and CARTITUDE-4 studies lead to the approval in earlier lines of therapy.

It is currently believed that ultimately all patients with relapsed/refractory multiple myeloma experience relapse after anti-BCMA CAR T-cell therapies. There is a plethora of CAR T-cell therapies targeting novel antigens, with the aim to overcome current CAR T-cell resistance. In this review, we will summarize current evidence of novel antigens and their clinical potential.

Together with current CAR T-cell therapy and T-cell engagers, these approaches might lead us to the next frontier in multiple myeloma: total immunotherapy and the road to chemotherapy-free cure.

论文信息

作者
Gagelmann N、Merz M
单位
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany. Electronic address: nico.gagelmann@posteo.de.Germany
文献类型
综述
期刊
Seminars in hematology2024 Oct
原文标识
PubMed 39095225 · DOI 10.1053/j.seminhematol.2024.07.002