文章：

新诊断多发性骨髓瘤患者持续治疗和维持治疗方法的进展

Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma

原文发布日期：2020-02-13

DOI: 10.1038/s41408-020-0273-x

类型: Review Article

开放获取: 是

英文摘要：

The evolving paradigm of continuous therapy and maintenance treatment approaches in multiple myeloma (MM) offers prolonged disease control and improved outcomes compared to traditional fixed-duration approaches. Potential benefits of long-term strategies include sustained control of disease symptoms, as well as continued cytoreduction and clonal control, leading to unmeasurable residual disease and the possibility of transforming MM into a chronic or functionally curable condition. “Continuous therapy” commonly refers to administering a doublet or triplet regimen until disease progression, whereas maintenance approaches typically involve single-agent or doublet treatment following more intensive prior therapy with autologous stem cell transplant (ASCT) or doublet, triplet, or even quadruplet induction therapy. However, the requirements for agents and regimens within these contexts are similar: treatments must be tolerable for a prolonged period of time, should not be associated with cumulative or chronic toxicity, should not adversely affect patients’ quality of life, should ideally be convenient with a minimal treatment burden for patients, and should not impact the feasibility or efficacy of subsequent treatment at relapse. Multiple agents have been and are being investigated as long-term options in the treatment of newly diagnosed MM (NDMM), including the immunomodulatory drugs lenalidomide and thalidomide, the proteasome inhibitors bortezomib, carfilzomib, and ixazomib, and the monoclonal antibodies daratumumab, elotuzumab, and isatuximab. Here we review the latest results with long-term therapy approaches in three different settings in NDMM: (1) maintenance treatment post ASCT; (2) continuous frontline therapy in nontransplant patients; (3) maintenance treatment post-frontline therapy in the nontransplant setting. We also discuss evidence from key phase 3 trials. Our review demonstrates how the paradigm of long-term treatment is increasingly well-established across NDMM treatment settings, potentially resulting in further improvements in patient outcomes, and highlights key clinical issues that will need to be addressed in order to provide optimal benefit.
 

摘要翻译： 

与传统固定疗程疗法相比，多发性骨髓瘤（MM）中不断发展的持续治疗和维持治疗模式能够延长疾病控制时间并改善预后。长期治疗策略的潜在益处包括：持续控制疾病症状、实现持续的肿瘤细胞减灭和克隆控制，从而达到无法检测的残留病变水平，并有可能将多发性骨髓瘤转化为慢性病或功能性治愈状态。“持续治疗”通常指使用双药或三药方案直至疾病进展，而“维持治疗”主要指自体干细胞移植（ASCT）后、或经过双药/三药/四药诱导强化治疗后采用单药或双药进行的治疗。然而，这两种治疗模式对药物和方案的要求相似：治疗方案需长期耐受性好、不产生累积性或慢性毒性、不影响患者生活质量、理想情况下应便捷且治疗负担最小化，且不影响复发后后续治疗的可行性或疗效。目前已有多种药物被作为新诊断多发性骨髓瘤（NDMM）的长期治疗选择进行研究，包括免疫调节药物来那度胺和沙利度胺，蛋白酶体抑制剂硼替佐米、卡非佐米和伊沙佐米，以及单克隆抗体达雷妥尤单抗、埃罗妥珠单抗和伊沙妥昔单抗。本文综述了新诊断多发性骨髓瘤三种不同场景下长期治疗方案的最新研究结果：（1）ASCT后维持治疗；（2）非移植患者的前线持续治疗；（3）非移植环境下前线治疗后的维持治疗。同时讨论了关键3期试验的证据。本综述揭示了长期治疗模式如何在NDMM各类治疗场景中日益巩固，可能进一步改善患者预后，并强调了为实现最佳疗效所需解决的关键临床问题。

原文链接：

Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma