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）生存期的一个公认替代标志物。本文通过免疫球蛋白基因二代测序技术，汇报单一机构评估MRD的经验，以及治疗反应深度与克隆多样性对大型MM患者群体临床结局的长期影响；我们对加州大学旧金山分校2008年至2020年诊断的482例MM患者进行了回顾性分析。MRD评估采用二代测序技术。无进展生存期曲线通过Kaplan-Meier法绘制。在新诊断组中，304例患者中有119例至少一次达到10−6水平的MRD阴性。与持续不同水平MRD阳性的患者相比，这些患者的无进展生存期显著延长（p > 0.0001）。在复发疾病组中，178例患者中有64例达到10−6水平的MRD阴性，其无进展生存期较持续MRD阳性的患者延长（p = 0.03）。通过人工智能定义了MRD动态变化的三种类型：（A）连续≥3次样本均保持MRD阴性的患者，（B）克隆持续下降但仍可检测的患者，（C）克隆数量增加或保持稳定的患者。A组和B组的无进展生存期较C组显著延长（p < 10−7）。在MRD阳性但尚未复发的患者中，其克隆多样性高于MRD阳性且已复发的患者。MRD动态变化能准确预测疾病演变并指导临床决策。克隆多样性可补充MRD评估，以提升多发性骨髓瘤预后预测的准确性。
肿瘤(癌症)患者之家