Applied Cancer Research and Drug Discovery, Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, AZ.
Clin Lymphoma Myeloma Leuk. 2020 Jan;20(1):1-7. doi: 10.1016/j.clml.2019.09.621. Epub 2019 Oct 9.
The advent of new, more effective, and less toxic therapies has revolutionized the management of multiple myeloma in the past decade. Despite the availability of new treatments, most patients with multiple myeloma will become refractory to the therapies that currently comprise the hematologic standard of care for the malignancy, including proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies. Moreover, in recent years, a new subset of patients with multiple myeloma refractory to all 3 of these agents has emerged. This population, for whom a clear treatment paradigm has remained undefined, has been characterized by poor survival outcomes. The current approaches to the treatment of triple-class refractory disease are limited and include conventional chemotherapy, salvage autologous stem cell transplantation, and recycling previous regimens, each of which have generally had short-lived efficacy. It is anticipated that additional agents will be available for triple-refractory disease in the near future, including selinexor, chimeric antigen receptor T-cell therapy, and next-generation monoclonal antibodies. The development and further refinement of novel treatments for this subset of patients should be considered a key clinical and research priority.
在过去的十年中，新的、更有效和毒性更低的疗法的出现彻底改变了多发性骨髓瘤的治疗方法。尽管有新的治疗方法，但大多数多发性骨髓瘤患者将对目前构成血液学标准治疗恶性肿瘤的治疗方法产生耐药性，包括蛋白酶体抑制剂、免疫调节剂和单克隆抗体。此外，近年来，出现了一种新的多发性骨髓瘤亚群，对这 3 种药物均耐药。对于这群人，明确的治疗模式仍未确定，其生存结果较差。目前对 3 类耐药疾病的治疗方法有限，包括常规化疗、挽救性自体干细胞移植和重复以前的方案，这些方案通常疗效短暂。预计在不久的将来，针对 3 类耐药疾病将有更多的药物可用，包括 selinexor、嵌合抗原受体 T 细胞疗法和下一代单克隆抗体。为这部分患者开发和进一步完善新的治疗方法应被视为一个关键的临床和研究重点。
