Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Department of Medicine, Harvard Medical School, Broad Institute of MIT & Harvard, Boston, Massachusetts 02215, USA.
Cold Spring Harb Perspect Med. 2021 Jul 1;11(7):a034900. doi: 10.1101/cshperspect.a034900.
Even though multiple myeloma (MM) is still considered incurable, the therapeutic management of this disease has undergone a major transformation over the last two decades, with several new classes of therapeutics and diverse options for their combined use in many different regimens that have contributed to major improvement in overall survival of patients. This review discusses key themes underlying the pharmacological and immune-based therapies that represent the cornerstones of this progress. A major part of the clinical progress achieved by these classes' therapeutics has depended on the targeting of molecular pathways with distinct or preferential roles for the biology of plasma cells-normal or malignant-and the ability of many of these agents to be incorporated into combination regimens that exhibit enhanced antimyeloma responses, without precipitating acceptable levels of toxicity. This review also discusses why these advances have not yet translated into curative outcomes and how these remaining barriers could be overcome.
虽然多发性骨髓瘤(MM)仍然被认为是无法治愈的,但在过去的二十年中,这种疾病的治疗管理已经发生了重大转变,出现了几类新的治疗药物,并且在许多不同的方案中可以将它们联合使用,这有助于患者的总生存率得到显著提高。本综述讨论了构成这些进展基础的药理学和免疫治疗的关键主题。这些治疗药物的临床进展在很大程度上取决于针对具有不同或优先作用的分子途径的靶向治疗,这些途径在浆细胞生物学(正常或恶性)中发挥作用,并且许多这些药物能够被纳入联合方案中,从而增强抗骨髓瘤反应,而不会引发可接受的毒性水平。本综述还讨论了为什么这些进展尚未转化为治愈结果,以及如何克服这些剩余的障碍。