Yan Wenqiang, Shi Lihui, Xu Jingyu, Li Lingna, Cui Jian, Liu Yuntong, Zhou Jieqiong, Du Chenxing, Yu Tengteng, Zhang Shuaishuai, Lv Rui, Sui Weiwei, Deng Shuhui, Li Xiaoqing, Du Xin, Xu Yan, Zou Dehui, Qiu Lugui, Hao Mu, An Gang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
Tianjin Institutes of Health Science, Tianjin, 301600, China.
Leukemia. 2024 Oct;38(10):2235-2245. doi: 10.1038/s41375-024-02366-9. Epub 2024 Aug 2.
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.
与肿瘤浆细胞相互竞争的残留正常浆细胞（NPCs）在多发性骨髓瘤中发挥着重要作用。然而，目前缺乏对残留NPCs进行大规模队列研究，尤其是在微小残留病（MRD）阶段。在本研究中，我们对来自NICHE队列（NCT04645199）的1363例骨髓瘤患者整个疾病过程中残留NPCs的临床意义进行了全面调查。我们的结果显示，基线NPCs比例高（≥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、免疫球蛋白缺乏和高危细胞遗传学的发生率降低。重要的是，诊断或复发时高残留NPCs比例与良好的生存独立相关。在不可检测的MRD时，NPCs的高绝对百分比与更好的临床获益和免疫重建相关。在MRD阳性阶段，基于NPCs比例（<50%、50-90%、≥90%）分组比残留肿瘤对数水平显示出更好的风险分层。基于时间依赖性NPCs比例趋势，我们开发了一种动态MRD模型，将患者分为具有不同纵向趋势的三组，导致不同的预后。总体而言，残留NPCs不仅作为风险分层的有价值的补充生物标志物，而且为MRD的重新分类和动力学提供了有价值的见解。
