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.

中文翻译：

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新诊断的多发性骨髓瘤患者持续治疗和维持治疗方法的进展。

与传统的固定疗程方法相比，多发性骨髓瘤 (MM) 持续治疗和维持治疗方法不断发展的范式提供了更长的疾病控制时间和更好的结果。长期策略的潜在好处包括持续控制疾病症状，以及持续的细胞减灭和克隆控制，从而导致无法测量的残留疾病，并有可能将 MM 转变为慢性或功能上可治愈的疾病。“连续治疗”通常是指施用双联或三联方案直至疾病进展，而维持方法通常涉及在使用自体干细胞移植（ASCT）或双联、三联甚至四联诱导的更强化的先前治疗之后进行单剂或双联治疗。治疗。然而，这些背景下对药物和治疗方案的要求是相似的：治疗必须能够长期耐受，不应与累积或慢性毒性相关，不应对患者的生活质量产生不利影响，理想情况下应方便患者的治疗负担最小，并且不应影响复发时后续治疗的可行性或疗效。多种药物已经和正在研究作为新诊断 MM (NDMM) 治疗的长期选择，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、埃洛妥珠单抗、和伊沙妥昔单抗。在这里，我们回顾了 NDMM 三种不同情况下长期治疗方法的最新结果：（1）ASCT 后维持治疗；(2)非移植患者的持续一线治疗；(3) 非移植环境中一线治疗后的维持治疗。我们还讨论了关键的第三阶段试验的证据。我们的综述展示了长期治疗范式如何在 NDMM 治疗环境中日益完善，有可能进一步改善患者的治疗结果，并强调需要解决的关键临床问题，以提供最佳效益。