上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2025, Vol. 45 ›› Issue (7): 807-814.doi: 10.3969/j.issn.1674-8115.2025.07.001

• 多发性骨髓瘤专题 •    下一篇

免疫不全麻痹在新诊断多发性骨髓瘤患者中的动态变化及预后意义

严治, 吴星玥, 姚卫芹, 颜灵芝, 金松, 商京晶, 施晓兰, 吴德沛, 傅琤琤()   

  1. 苏州大学附属第一医院血液科，苏州 215006
  • 收稿日期:2025-02-13 接受日期:2025-05-07 出版日期:2025-07-28 发布日期:2025-07-28
  • 通讯作者: 傅琤琤，主任医师，博士；电子信箱：fuchengchengsz@163.com。
  • 基金资助:
    国家自然科学基金(82270210);苏州市基础研究试点项目(SSD2024088)

Dynamic changes and prognostic significance of immunoparesis in newly diagnosed multiple myeloma patients

YAN Zhi, WU Xingyue, YAO Weiqin, YAN Lingzhi, JIN Song, SHANG Jingjing, SHI Xiaolan, WU Depei, FU Chengcheng()   

  1. Department of Haematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
  • Received:2025-02-13 Accepted:2025-05-07 Online:2025-07-28 Published:2025-07-28
  • Contact: FU Chengcheng, E-mail: fuchengchengsz@163.com.
  • Supported by:
    National Natural Science Foundation of China(82270210);Suzhou Basic Research Pilot Project Project(SSD2024088)

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摘要：

目的·检测多发性骨髓瘤（multiple myeloma，MM）患者在新诊断和诱导治疗后免疫球蛋白表达水平，探索免疫球蛋白表达水平及其动态变化与疗效、感染发生及预后的关系。方法·纳入分析2018年8月至2020年9月于苏州大学附属第一医院血液科收治的142例MM患者的临床资料，评估其基线免疫球蛋白水平及硼替佐米-来那度胺-地塞米松（bortezomib-lenalidomide-dexamethasone，VRD）方案诱导治疗后的变化。免疫不全麻痹定义为未受累免疫球蛋白水平低于实验室参考值下限，并按其程度对患者分层（轻度、中度、重度、极重度）。采用方差分析、秩和检验、χ2检验等方法分析免疫不全麻痹与基线特征的相关性，并根据其动态变化，分析免疫不全麻痹改善与疗效、感染发生、预后的关系。结果·初诊MM患者正常免疫球蛋白严重减少。128例（90.1%）患者存在免疫不全麻痹，其中重度及以上免疫不全麻痹占76.1%。有广泛免疫不全麻痹（全部未受累免疫球蛋白水平低于参考值下限）患者更容易出现重度及以上免疫不全麻痹（P<0.05）。不同程度免疫不全麻痹MM患者的年龄、性别、是否重度肾功能不全及是否遗传学高危差异均无统计学意义（P>0.05），但其MM分期（P=0.008）和分型（P=0.010）差异均有统计学意义。免疫不全麻痹严重者多处于修订的国际分期系统（Revised International Staging System，R-ISS）Ⅱ/Ⅲ期和IgG型。MM患者受累免疫球蛋白或轻链的水平与正常免疫球蛋白水平呈负相关（P<0.05）。完成诱导治疗后MM患者免疫不全麻痹改善的程度与诱导治疗效果呈正相关（P=0.006）。诱导治疗过程中，MM患者感染发生率（26.8%）较高，免疫不全麻痹与感染无相关性（P>0.05）。完成诱导治疗后，MM患者免疫不全麻痹改善者有更长的无进展生存期（progression-free survival，PFS）（中位PFS：当前随访时间下未达到vs 38个月，P=0.025），对总生存期（overall survival，OS）无显著影响（P=0.450）。结论·MM患者初诊时免疫不全麻痹普遍存在且较严重，免疫不全麻痹程度与疾病分型及分期相关。VRD治疗可部分逆转免疫抑制，免疫不全麻痹改善程度与MM缓解深度呈正相关，并提示PFS获益。感染风险独立于免疫不全麻痹，需综合防控。体液免疫缺陷状态或可作为MM预后评估指标，但其对OS的影响需进一步验证。

关键词: 多发性骨髓瘤, 免疫球蛋白, 体液免疫, 免疫不全麻痹, 感染, 预后

Abstract:

Objective ·To detect immunoglobulin (Ig) expression levels in newly diagnosed multiple myeloma (MM) patients before and after induction therapy, and to explore the clinical significance of Ig expression levels and their dynamic changes in relation to treatment efficacy, infection occurrence, and prognosis. Methods ·Clinical data from 142 MM patients treated at the Department of Hematology, The First Affiliated Hospital of Soochow University between August 2018 and September 2020 were analyzed. Baseline Ig expression levels and post-induction changes following bortezomib-lenalidomide-dexamethasone (VRD) regimen were assessed. Immunoparesis was defined as uninvolved Igs below the laboratory lower limit of normal. Patients were stratified by immunoparesis severity (mild, moderate, severe, extremely severe). ANOVA, rank-sum tests, and χ2 tests were used to analyze correlations with baseline characteristics. The relationship between the improvement in immunoparesis and the induction efficacy, infection occurrence, and prognosis was analyzed based on the dynamic changes in immunoparesis. Results ·Normal Igs were severely reduced in newly diagnosed MM patients. Immunoparesis was present in 128 patients (90.1%), with severe or extremely severe immunoparesis accounting for 76.1%. Patients with extensive immunoparesis (all uninvolved Ig levels below the lower normal limit) were more likely to have severe immunoparesis (P<0.05). There were no statistically significant differences in age,gender, presence of severe renal insufficiency, and high-risk cytogenetics among MM patients with different degrees of immunoparesis (P>0.05), but there were statistically significant differences in MM staging (P=0.008) and typing (P=0.010). Most patients with severe immunoparesis were at stage Ⅱ/Ⅲ based on the Revised International Staging System (R-ISS) and were of the IgG type. At diagnosis, the levels of the involved Ig or light chain were negatively correlated with normal Ig levels (P<0.05). Improvement in immunoparesis after induction therapy was positively correlated with treatment response (P=0.006). The infection rate was high (26.8%), but no significant correlation was found between immunoparesis and infection occurrence (P>0.05). After induction therapy, patients showing improvement in immunoparesis had significantly longer progression-free survival (PFS) (median PFS: not reached vs 38 months, P=0.025), but no significant impact on overall survival (OS) was observed (P=0.450). Conclusion ·Immunoparesis is common and severe in newly diagnosed MM patients, with severity correlating with disease stage and subtype. VRD therapy can partially reverse immunoparesis, and improvement is positively associated with treatment response and PFS benefit. Infection risk appears unrelated to immunoparesis severity and warrants comprehensive prevention strategies. Humoral immune deficiency may serve as a prognostic indicator in MM, but its impact on OS requires further investigation.

Key words: multiple myeloma, immunoglobulin, humoral immunity, immunoparesis, infection, prognosis

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