The assessment of measurable residual disease (MRD) in bone marrow has proven of prognostic relevance in patients with multiple myeloma (MM). Nevertheless, and unlike other hematologic malignancies, the use of MRD results to make clinical decisions in MM has been underexplored to date. In this retrospective study, we present the results from a multinational and multicenter series of 400 patients with MRD monitoring during front-line therapy with the aim of exploring how clinical decisions made based on those MRD results affected outcomes. As expected, achievement of MRD negativity at any point was associated with improved PFS versus persistent MRD positivity (median PFS 104 vs. 45 months, p < 0.0001). In addition, however, 67 out of 400 patients underwent a clinical decision (treatment discontinuation, intensification or initiation of a new therapy) based on MRD results. Those patients in whom a treatment change was made showed a prolonged PFS in comparison with those 333 patients in which MRD results were not acted upon (respectively, mPFS 104 vs. 62 months, p = 0.005). In patients who achieved MRD negativity during maintenance (n = 186) on at least one occasion, stopping therapy in 24 patients vs. continuing in 162 did not alter PFS (mPFS 120 months vs. 82 months, p = 0.1). Most importantly, however, in patients with a positive MRD during maintenance (n = 214), a clinical decision (either intensification or change of therapy) (n = 43) resulted in better PFS compared to patients in whom no adjustment was made (n = 171) (mPFS NA vs. 39 months, p = 0.02). Interestingly, there were no significant differences when MRD was assessed by flow cytometry or by next-generation sequencing. Herein, we find that MRD is useful in guiding clinical decisions during initial therapy and has a positive impact on PFS in MM patients. This potentially opens a new dimension for the use of MRD in MM, but this role still remains to be confirmed in prospective, randomized clinical trials.

中文翻译：

---

根据可测量的残留病灶做出临床决策可改善多发性骨髓瘤的预后

骨髓中可测量残留病灶 (MRD) 的评估已证明与多发性骨髓瘤 (MM) 患者的预后相关。然而，与其他血液系统恶性肿瘤不同的是，迄今为止，尚未充分探索使用 MRD 结果在 MM 中做出临床决策。在这项回顾性研究中，我们展示了在一线治疗期间对 400 名患者进行 MRD 监测的多国和多中心系列结果，目的是探索基于这些 MRD 结果做出的临床决策如何影响结果。正如预期的那样，在任何时候实现 MRD 阴性都与改善 PFS 与持续 MRD 阳性相关（中位 PFS 104 个月与 45 个月，p < 0.0001）。然而，此外，400 名患者中有 67 名接受了临床决定（停止治疗，强化或开始新疗法）基于 MRD 结果。与未采取 MRD 结果的 333 名患者相比，那些改变治疗的患者显示出延长的 PFS（分别为 mPFS 104 与 62 个月，p = 0.005）。在维持期间（n = 186）至少有一次达到 MRD 阴性的患者中，24 名患者停止治疗与 162 名继续治疗并没有改变 PFS（mPFS 120 个月与 82 个月，p = 0.1）。然而，最重要的是，在维持期间 MRD 阳性的患者 (n = 214) 中，与未进行调整的患者相比，临床决策（强化或改变治疗）（n = 43）导致更好的 PFS（n = 171)（mPFS NA 对比 39 个月，p = 0.02）。有趣的是，当通过流式细胞术或下一代测序评估 MRD 时，没有显着差异。在此，我们发现 MRD 可用于指导初始治疗期间的临床决策，并对 MM 患者的 PFS 产生积极影响。这可能为 MRD 在 MM 中的应用开辟了一个新的维度，但这一作用仍有待前瞻性随机临床试验证实。