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多发性骨髓瘤的新型治疗选择

Novel Treatment Options for Multiple Myeloma.

作者信息

Portuguese Andrew J, Banerjee Rahul, Chen GuiZhen, Reddi Swetha, Cowan Andrew J

机构信息

Fred Hutchinson Cancer Center, Seattle, WA.

University of Washington, Seattle, WA.

出版信息

JCO Oncol Pract. 2025 Jul;21(7):950-961. doi: 10.1200/OP-24-00752. Epub 2025 Jan 7.

Abstract

Multiple myeloma (MM), the second most common hematologic malignancy in the United States, is characterized by repeated cycles of remission and relapse, with increasing resistance to treatment after each line of therapy. Despite the virtually incurable nature of MM, recent therapeutic breakthroughs have fundamentally reshaped its treatment landscape. This review explores evolving care paradigms, spanning from newly diagnosed MM to relapsed or refractory disease. In the frontline setting, treatment strategies have shifted beyond their traditional emphasis on autologous stem-cell transplant eligibility to a broader categorization of patients on the basis of their suitability for quadruplet therapy. In the relapsed/refractory setting, novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies, have revolutionized treatment, offering new hope for patients with previously limited options. Precision medicine is playing a growing role in MM treatment, with venetoclax showing significant efficacy in patients with t(11;14) translocation, advancing targeted therapy for this subgroup. On the horizon, investigational CAR-T products and cereblon E3 ligase modulators, such as mezigdomide and iberdomide, may provide faster, more durable responses compared with current therapies. In addition, belantamab mafodotin, an antibody-drug conjugate withdrawn from the US market in 2022, is on the verge of reapproval after positive results from recent randomized trials. While these therapies offer significant potential, challenges remain in managing toxicity, ensuring treatment accessibility, and optimizing sequencing strategies. As the therapeutic arsenal expands, the need for personalized MM treatment plans that balance efficacy with quality of life becomes even more essential.

摘要

多发性骨髓瘤(MM)是美国第二常见的血液系统恶性肿瘤,其特征是缓解和复发的反复循环,且每一线治疗后对治疗的耐药性都会增加。尽管MM本质上几乎无法治愈,但最近的治疗突破已从根本上重塑了其治疗格局。本综述探讨了不断演变的护理模式,涵盖从新诊断的MM到复发或难治性疾病。在一线治疗中,治疗策略已从传统上对自体干细胞移植适用性的强调,转向根据患者对四联疗法的适用性进行更广泛的分类。在复发/难治性治疗中,新型免疫疗法,包括嵌合抗原受体T细胞(CAR-T)疗法和双特异性抗体,彻底改变了治疗方式,为以前选择有限的患者带来了新希望。精准医学在MM治疗中发挥着越来越重要的作用,维奈克拉在t(11;14)易位患者中显示出显著疗效,推动了该亚组的靶向治疗。展望未来,研究性CAR-T产品和脑啡肽E3连接酶调节剂,如美齐多胺和艾伯多胺,与现有疗法相比,可能会提供更快、更持久的反应。此外,抗体药物偶联物贝兰他单抗莫福汀于2022年从美国市场撤出,在最近的随机试验取得阳性结果后,即将重新获批。虽然这些疗法具有巨大潜力,但在管理毒性、确保治疗可及性和优化治疗顺序策略方面仍存在挑战。随着治疗手段的不断扩展,制定平衡疗效与生活质量的个性化MM治疗方案的需求变得更加迫切。

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