Residual normal plasma cells (NPCs), which compete with tumor plasma cells, play an important role in multiple myeloma. However, large-scale cohort studies investigating residual NPCs, especially at the minimal residual disease (MRD) phase, are currently lacking. In this study, we conducted a comprehensive investigation into the clinical significance of residual NPCs throughout the entire disease course in 1363 myeloma patients from the NICHE cohort (NCT04645199). Our results revealed that myeloma patients with high baseline NPCs ratio (≥5%) exhibited distinct indolent features, characterized by lower tumor burden, reduced frequencies of cytopenia, immunoparesis, and high-risk cytogenetics. Importantly, high residual NPCs ratio at diagnosis or relapse was independently associated with favorable survival. High absolute percentages of NPCs at undetectable MRD were related with superior clinical benefit and immune reconstitution. At MRD-positive phases, grouping based on NPCs ratio (<50%, 50–90%, ≥90%) demonstrated better risk stratification compared to residual tumor log levels. Based on the time-dependent NPCs ratio trend, we developed a dynamic MRD model that classifies patients into three groups with diverse longitudinal trends, leading to distinct prognoses. Collectively, residual NPCs serves not only as a valuable complementary biomarker for risk stratification but also provides valuable insights on reclassifications and kinetics of MRD.

残留的正常浆细胞（NPC）与肿瘤浆细胞竞争，在多发性骨髓瘤中发挥重要作用。然而，目前缺乏调查残留鼻咽癌的大规模队列研究，特别是在微小残留病（MRD）阶段。在这项研究中，我们对来自 NICHE 队列 (NCT04645199) 的 1363 名骨髓瘤患者的整个病程中残留 NPC 的临床意义进行了全面调查。我们的结果显示，基线 NPC 比例较高（≥5%）的骨髓瘤患者表现出明显的惰性特征，其特点是肿瘤负荷较低、血细胞减少、免疫麻痹和高风险细胞遗传学发生率降低。重要的是，诊断或复发时的高残留 NPC 比率与良好的生存率独立相关。未检测到 MRD 的 NPC 绝对百分比高与卓越的临床效益和免疫重建相关。在 MRD 阳性阶段，基于 NPC 比率（<50%、50–90%、≥90%）的分组显示出与残留肿瘤日志水平相比更好的风险分层。根据时间依赖性 NPC 比率趋势，我们开发了动态 MRD 模型，将患者分为具有不同纵向趋势的三组，从而产生不同的预后。总的来说，残留的 NPC 不仅可以作为风险分层的有价值的补充生物标志物，而且还可以为 MRD 的重新分类和动力学提供有价值的见解。