Swan Dawn, Madduri Deepu, Hocking Jay
Department of Haematology, Austin Health, Melbourne, VIC, Australia.
Department of Medicine, Blood and Marrow Transplantation, Stanford Hospital, Palo Alto, CA, USA.
Blood Cancer J. 2024 Nov 26;14(1):206. doi: 10.1038/s41408-024-01191-8.
The treatment of multiple myeloma has changed dramatically in recent years, with huge strides forward made in the field. Chimeric antigen receptor T-cell therapy targeting the B cell maturation antigen (BCMA) is now widely approved in relapsed refractory patients and is moving into earlier treatment lines. In this review, we discuss the evidence underpinning current regulatory approvals and consider mechanisms through which CAR-T cell efficacy could be improved. These include tackling BCMA-loss, harnessing the immunosuppressive tumour microenvironment, manufacturing concerns including the potential role of other cellular sources, safety issues such as cytokine release syndrome and neurotoxicity, and optimal patient selection.
近年来，多发性骨髓瘤的治疗发生了巨大变化，该领域取得了巨大进展。靶向B细胞成熟抗原（BCMA）的嵌合抗原受体T细胞疗法现已在复发难治性患者中广泛获批，并正在进入更早的治疗阶段。在这篇综述中，我们讨论了支持当前监管批准的证据，并思考可提高CAR-T细胞疗效的机制。这些机制包括解决BCMA缺失问题、利用免疫抑制性肿瘤微环境、解决生产方面的问题（包括其他细胞来源的潜在作用）、解决诸如细胞因子释放综合征和神经毒性等安全问题，以及优化患者选择。
