Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN.
Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):518-524. doi: 10.1182/asheducation-2017.1.518.
Considerable progress has been made in the treatment of multiple myeloma in the past decade with median survival for the disease improving significantly. This has come through a combination of better understanding of the disease biology and coordinated research into new treatment approaches including better supportive care. However, patients eventually become refractory to available treatments and succumb to the disease, highlighting the need to develop new treatment approaches. The genetic heterogeneity in the disease and clonal evolution under treatment pressure underlie the development of resistance, underscoring the need to develop more effective therapies that can eradicate the disease at initial treatment as well as the need for new classes of drugs with varying mechanisms of action. To this end, there has been intense focus on exploring novel approaches to therapy including small-molecule inhibitors targeting specific abnormalities, immune therapies including monoclonal antibodies and adaptive T-cell therapy, as well as epigenetic approaches. Although many of these drugs are in the early stages of clinical development, the early data appear to be very promising. Many of these drugs can be safely and effectively combined with the current treatment classes such as proteasome inhibitors and immunomodulatory drugs, further enhancing the treatment options for myeloma.
在过去的十年中,多发性骨髓瘤的治疗取得了重大进展,疾病的中位生存期显著改善。这是通过更好地了解疾病生物学和协调研究新的治疗方法(包括更好的支持性护理)相结合实现的。然而,患者最终会对现有治疗产生耐药性并死于该疾病,这凸显了开发新治疗方法的必要性。疾病的遗传异质性和治疗压力下的克隆进化是耐药性发展的基础,这强调了需要开发更有效的治疗方法,不仅在初始治疗时能够根除疾病,还需要具有不同作用机制的新药类。为此,人们强烈关注探索新的治疗方法,包括针对特定异常的小分子抑制剂、免疫疗法,包括单克隆抗体和适应性 T 细胞疗法,以及表观遗传学方法。尽管这些药物中的许多仍处于临床开发的早期阶段,但早期数据似乎非常有希望。许多这些药物可以与当前的治疗类别(如蛋白酶体抑制剂和免疫调节剂)安全有效地联合使用,进一步增强了骨髓瘤的治疗选择。