The standards of care for the initial treatment of patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose melphalan and autologous stem cell transplantation (HDM-ASCT) include highly active triplet and quadruplet regimens based on proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These regimens are resulting in improved outcomes and increasingly high rates of minimal residual disease (MRD)-negative responses without HDM-ASCT as part of the upfront therapy. Furthermore, recent randomized studies have shown that, while transplant-based approaches as a frontline therapy result in significantly longer progression-free survival compared to non-transplant approaches, this has not translated into an overall survival benefit. Given these developments, and in the context of the treatment burden of undergoing HDM-ASCT, in addition to the acute toxicities and long-term sequelae of HDM, which are associated with the genotoxicity of melphalan, there is an increasing rationale for considering deferring upfront HDM-ASCT in select transplant-eligible patients and saving it as a treatment option for later salvage therapy. Here, we review the latest clinical trial data on upfront or deferred HDM-ASCT and on the activity of quadruplet induction regimens, including rates of MRD-negative responses, and summarize emerging treatment approaches in the upfront setting such as the use of MRD-directed therapy and alternatives to HDM-ASCT.
对于适合接受大剂量马法兰联合自体干细胞移植（HDM-ASCT）的新诊断多发性骨髓瘤（NDMM）患者，其初始治疗标准方案包含以蛋白酶体抑制剂、免疫调节剂和单克隆抗体为基础的高活性三联及四联疗法。这些方案在不将HDM-ASCT作为前期治疗组成部分的情况下，仍能改善患者预后，并实现日益升高的微小残留病（MRD）阴性缓解率。此外，近期随机研究表明，虽然基于移植的一线治疗方案相较于非移植方案能显著延长无进展生存期，但并未转化为总生存获益。鉴于这些进展，结合HDM-ASCT的治疗负担、马法兰基因毒性相关的急性毒性及长期后遗症，对于部分适合移植的患者，推迟前期HDM-ASCT并将其保留作为后续挽救治疗选项的合理性日益凸显。本文综述了关于前期或延迟HDM-ASCT的最新临床试验数据，包括四联诱导方案的疗效及MRD阴性缓解率，并总结了当前新兴的前期治疗策略，如MRD导向疗法及HDM-ASCT的替代方案。
肿瘤(癌症)患者之家