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治疗复发/难治性多发性骨髓瘤的现有及正在研发的合成药物疗法。

Current and developing synthetic pharmacotherapy for treating relapsed/refractory multiple myeloma.

作者信息

Podar Klaus, Pecherstorfer Martin

机构信息

a Department of Internal Medicine , Karl Landsteiner University of Health Sciences, University Hospital , Krems , Austria.

出版信息

Expert Opin Pharmacother. 2017 Aug;18(11):1061-1079. doi: 10.1080/14656566.2017.1340942. Epub 2017 Jul 5.

DOI:10.1080/14656566.2017.1340942
PMID:28604120
Abstract

The introduction of novel agents has significantly improved multiple myeloma (MM) patient outcome during the last two decades. MM received the most drug approvals for any one malignancy during this time period, both in the United States as well as in Europe. Areas covered: Proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies are prototype drug classes, which target both specific MM cell functions, as well as the tumor supportive bone marrow microenvironment, and represent current cornerstones of MM therapy. Importantly, the unprecedented extent and frequency of durable responses, in relapsed/refractory multiple myeloma (RRMM), in particular, is predominantly based on the combinatorial use of these agents with conventional chemotherapeutics or representatives of other drug classes. This article will summarize past landmark discoveries in MM that led to the dramatic progress of today's clinical practice. Moreover, developing strategies will be discussed that are likely to yet improve patient outcome even further. Expert opinion: Despite significant therapeutic advancements, MM remains an incurable disease. With several novel agents in the preclinical and early clinical pipeline, among those novel CD38 and BCMA mAbs, immune checkpoint inhibitors, as well as ricolinostat, selinexor, venetoclax, CAR-T cells, and vaccines, further advances in MM patient outcome are expected in the near future.

摘要

在过去二十年中,新型药物的引入显著改善了多发性骨髓瘤(MM)患者的预后。在此期间,MM在美国和欧洲获得的药物批准数量超过了任何一种恶性肿瘤。涵盖领域:蛋白酶体抑制剂、免疫调节药物和单克隆抗体是典型的药物类别,它们既针对MM细胞的特定功能,也针对支持肿瘤的骨髓微环境,是目前MM治疗的基石。重要的是,尤其是在复发/难治性多发性骨髓瘤(RRMM)中,前所未有的持久缓解程度和频率主要基于这些药物与传统化疗药物或其他药物类别的代表药物联合使用。本文将总结MM过去具有里程碑意义的发现,这些发现推动了当今临床实践的巨大进步。此外,还将讨论可能进一步改善患者预后的发展策略。专家观点:尽管治疗取得了重大进展,但MM仍然是一种无法治愈的疾病。随着几种新型药物处于临床前和早期临床阶段,包括新型CD38和BCMA单克隆抗体、免疫检查点抑制剂以及ricolinostat、selinexor、venetoclax、嵌合抗原受体T细胞(CAR-T)和疫苗,预计在不久的将来MM患者的预后将取得进一步进展。

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