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多发性骨髓瘤的新兴免疫疗法。

Emerging immunotherapies in multiple myeloma.

机构信息

Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 East 74th Street, New York, NY 10021, USA

Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 East 74th Street, New York, NY 10021, USA.

出版信息

BMJ. 2020 Sep 21;370:m3176. doi: 10.1136/bmj.m3176.

Abstract

Despite considerable advances in treatment approaches in the past two decades, multiple myeloma remains an incurable disease. Treatments for myeloma continue to evolve with many emerging immunotherapies. The first immunotherapy used to treat hematologic cancers, including multiple myeloma, was an allogeneic stem cell transplant. In the mid-2000s, immunomodulatory drugs thalidomide, lenalidomide, and subsequently pomalidomide were proven to be effective in multiple myeloma and substantially improved survival. The next wave of immunotherapies for multiple myeloma included the monoclonal antibodies daratumumab and elotuzumab, which were approved by the Food and Drug Administration in 2015. Subsequently, a variety of immunotherapies have been developed for multiple myeloma, including chimeric antigen receptor T cells, bispecific antibodies, antibody drug conjugates, and checkpoint inhibitors. Many of these emerging treatments target the B cell maturation antigen, which is expressed on plasma cells, although several other novel receptors are also being studied. This review summarizes the evidence of these various immunotherapies, their mechanism of action, and data from clinical trials regarding the treatments' safety and efficacy.

摘要

尽管在过去的二十年中治疗方法有了很大的进步,但多发性骨髓瘤仍然是一种无法治愈的疾病。骨髓瘤的治疗方法仍在不断发展,许多新的免疫疗法不断涌现。第一种用于治疗血液系统癌症(包括多发性骨髓瘤)的免疫疗法是异体干细胞移植。在 21 世纪中期,免疫调节剂沙利度胺、来那度胺和随后的泊马度胺已被证明对多发性骨髓瘤有效,并显著提高了生存率。多发性骨髓瘤的下一波免疫疗法包括单克隆抗体达雷妥尤单抗和依洛珠单抗,它们于 2015 年获得美国食品和药物管理局的批准。随后,针对多发性骨髓瘤开发了多种免疫疗法,包括嵌合抗原受体 T 细胞、双特异性抗体、抗体药物偶联物和检查点抑制剂。这些新兴治疗方法中的许多都针对 B 细胞成熟抗原,该抗原在浆细胞上表达,尽管也在研究其他几个新的受体。这篇综述总结了这些各种免疫疗法的证据、它们的作用机制以及临床试验中关于这些治疗方法的安全性和疗效的数据。

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