Minimal residual disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). Here, we present a single institution’s experience assessing MRD by NGS of Ig genes and the long-term impact of depth of response as well as clonal diversity on the clinical outcome of a large population of MM patients; 482 MM patients at the University of California, San Francisco (UCSF) diagnosed from 2008 to 2020 were analyzed retrospectively. MRD assessment was performed by NGS. PFS curves were plotted by the Kaplan–Meier method. In the newly diagnosed group, 119 of 304, achieved MRD negativity at the level of 10⁻⁶ at least once. These patients had a prolonged PFS versus patients who were persistently MRD positive at different levels (p > 0.0001). In the relapsed disease group, 64 of 178 achieved MRD negativity at 10⁻⁶, and PFS was prolonged versus patients who remained MRD positive (p = 0.03). Three categories of MRD dynamics were defined by artificial intelligence: (A) patients with ≥3 consistently MRD negative samples, (B) patients with continuously declining but detectable clones, and (C) patients with either increasing or a stable number of clones. Groups A and B had a more prolonged PFS than group C (p < 10⁻⁷). Patients who were MRD positive and had not yet relapsed had a higher clonal diversity than those patients who were MRD positive and had relapsed. MRD dynamics can accurately predict disease evolution and drive clinical decision-making. Clonal Diversity could complement MRD assessment in the prediction of outcomes in MM.

微小残留病 （MRD） 评估是多发性骨髓瘤 （MM） 生存的已知替代标志物。在这里，我们介绍了一个机构通过 Ig 基因 NGS 评估 MRD 的经验，以及反应深度和克隆多样性对大量 MM 患者临床结果的长期影响;回顾性分析了 2008 年至 2020 年诊断的加州大学旧金山分校 （UCSF） 的 482 例 MM 患者。通过 NGS 进行 MRD 评估。PFS 曲线采用 Kaplan-Meier 方法绘制。在新诊断的组中，304 人中有 119 人至少一次达到 ^10-6 水平的 MRD 阴性。与在不同水平持续 MRD 阳性的患者相比，这些患者的 PFS 延长 （p > 0.0001）。在复发性疾病组中，178 例中有 64 例达到 ^10-6 的 MRD 阴性，与保持 MRD 阳性的患者相比，PFS 延长 （p = 0.03）。人工智能定义了三类 MRD 动力学：（A） 具有 ≥3 个持续 MRD 阴性样本的患者，（B） 具有持续下降但可检测到的克隆的患者，以及 （C） 克隆数量增加或稳定的患者。A 组和 B 组的 PFS 比 C 组更长 （p < 10⁻⁷）。MRD 阳性且尚未复发的患者比 MRD 阳性且已复发的患者具有更高的克隆多样性。MRD 动力学可以准确预测疾病演变并推动临床决策。克隆多样性可以在预测 MM 结果方面补充 MRD 评估。