Anti-ENA antibody positivity as a novel immunological marker for suboptimal treatment response and poor prognosis in multiple myeloma: A real-world cohort study

WU Zhenzhen; CAO Tingyong; FENG Youfan; ZHAO Li

doi:10.16016/j.2097-0927.202511108

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Anti-ENA antibody positivity as a novel immunological marker for suboptimal treatment response and poor prognosis in multiple myeloma: A real-world cohort study

Clinical Medicine | 更新时间：2026-02-23

- Anti-ENA antibody positivity as a novel immunological marker for suboptimal treatment response and poor prognosis in multiple myeloma: A real-world cohort study
- Journal of Army Medical University Vol. 48, Issue 3, Pages: 325-336(2026)
- 作者机构：
  
  1.兰州大学第一临床医学院，甘肃兰州
  2.兰州大学第二医院血液科，甘肃兰州
  3.甘肃省人民医院血液科，甘肃兰州
  4.兰州大学第一医院甘肃省血液病分子诊断与治疗临床医学研究中心，甘肃兰州
  5.兰州大学第一医院医学检验中心，甘肃兰州
- 作者简介：
  
  ZHAO Li，E-mail：zhaoli@lzu.edu.cn
- 基金信息：
  
  the Gansu Provincial Youth Science and Technology Foundation(25JRRA1029)
- DOI：10.16016/j.2097-0927.202511108
  CLC： R446.62;R730.7;R733.3
- Received：24 November 2025，
  
  Revised：2026-01-13，
  
  Accepted：14 January 2026，
  
  Published：15 February 2026
- 稿件说明：
移动端阅览
吴珍珍，曹婷雍，冯友繁，等.抗ENA抗体阳性作为多发性骨髓瘤治疗反应差与预后不良的新型免疫学标志：一项真实世界队列研究［J］.陆军军医大学学报，2026，48（03）：325-336.DOI：10.16016/j.2097-0927.202511108.

WU Z Z，CAO T Y，FENG Y F，et al.Anti-ENA antibody positivity as a novel immunological marker for suboptimal treatment response and poor prognosis in multiple myeloma： A real-world cohort study［J］.J Army Med Univ，2026，48（03）：325-336.DOI：10.16016/j.2097-0927.202511108.
吴珍珍，曹婷雍，冯友繁，等.抗ENA抗体阳性作为多发性骨髓瘤治疗反应差与预后不良的新型免疫学标志：一项真实世界队列研究［J］.陆军军医大学学报，2026，48（03）：325-336.DOI：10.16016/j.2097-0927.202511108. DOI：

WU Z Z，CAO T Y，FENG Y F，et al.Anti-ENA antibody positivity as a novel immunological marker for suboptimal treatment response and poor prognosis in multiple myeloma： A real-world cohort study［J］.J Army Med Univ，2026，48（03）：325-336.DOI：10.16016/j.2097-0927.202511108. DOI：

摘要

目的

旨在分析伴有自身抗体谱阳性（positive autoantibody profiles， PA）的多发性骨髓瘤（multiple myeloma， MM）患者的临床特征及其与治疗反应和预后间的关系。

方法

采用单中心回顾性队列研究，纳入2015年4月至2025年4月于兰州大学第一医院甘肃省血液病分子诊断与治疗临床医学研究中心完成自身抗体谱检查的189例MM患者。随访截至2025年8月1日。依据自身抗体谱检测结果，将患者分为自身抗体谱阴性（negative autoantibody profiles， NA）组与PA组，并比较2组患者的基线特征与治疗反应。治疗反应的评估包括总体反应率（overall response rate，ORR）、完全缓解（complete response，CR）率、部分缓解（partial response， PR）率、无效率及抗CD38单抗、自体造血干细胞移植（autologous hematopoietic stem cell transplantation， auto-HSCT）的关键治疗策略的应用率。进一步将PA组患者按抗体谱亚型分为抗核抗体（antinuclear antibody， ANA）谱、抗可提取核抗原（extractable nuclear antigen， ENA）抗体谱以及抗中性粒细胞胞质抗体（antineutrophil cytoplasmic antibody， ANCA）谱阳性3个亚型，分析其预后差异。采用Kaplan-Meier生存曲线计算中位生存时间，采用Cox回归分析预后影响因素。

结果

纳入的189例MM患者中PA组57（30.16%）例，NA组132（69.84%）例。所有患者接受治疗，有58（30.69%）例患者接受了抗CD38单抗治疗，57（30.16%）例患者接受auto-HSCT治疗。诱导治疗后MM患者的ORR为75.66%（143/189），CR为32.28%（61/189），PR为43.39%（82/189）。PA组患者的CR显著低于NA组（21.05%

37.12%，

=0.031）。当中位随访时间为39（16，59）个月时，此队列患者的中位无进展生存期（progression-free survival， PFS）为37（16，58）个月，但总生存期（overall survival， OS）仍尚未达到其中位值。相较于NA组，PA组患者的PFS显著缩短（31

43个月，

=0.048）。根据自身抗体谱类型进行亚组分析，抗ENA抗体谱阳性组患者中位OS较阴性组显著缩短（41

61个月，

=0.038）；中位PFS也显著缩短（28

41个月，

=0.001）。ANA谱与ANCA谱阳性组与阴性组患者的中位PFS与中位OS间均无显著差异。Cox分析显示，抗ENA抗体谱阳性（

=0.004）、男性（

0.001）是MM患者OS的独立危险因素，而诱导治疗后达到CR（

=0.002）及抗CD38单抗（

=0.008）治疗为MM患者OS的独立保护因素。在PFS方面，男性（

0.001）与抗ENA抗体谱阳性（

0.001）是独立危险因素，而纤维蛋白原水平升高（

=0.011）、诱导治疗后达到CR（

=0.009）及抗CD38单抗（

=0.011）治疗是其独立保护因素。

结论

PA的MM患者诱导治疗反应与远期预后均较差，而抗ENA抗体谱阳性是MM患者OS和PFS的独立危险因素。

Abstract

Objective

To evaluate the clinical characteristics and their associations with treatment response and prognosis in multiple myeloma (MM) patients with positive autoantibody profiles (PA).

Methods

This single-center retrospective cohort study enrolled 189 MM patients who had undergone the autoantibody profile tests at the Gansu Provincial Clinical Medical Research Center for Molecular Diagnosis and Treatment of Hematological Diseases

the First Hospital

Lanzhou University

from April 2015 to April 2025. Follow-up data were collected until August 1

2025. Based on the autoantibody profile results

patients were categorized into a negative autoantibody profiles group (NA) and a PA group for comparison of baseline characteristics and treatment responses between the two groups. The assessment of treatment response included the overall response rate (ORR)

complete response (CR) rate

partial response (PR) rate

non-response rate

and the utilization rates of key therapeutic strategies

such as anti-CD38 monoclonal antibody therapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Furthermore

the PA group patients were stratified into three subtypes based on antibody profiles: antinuclear antibody (ANA)-positive

anti-extractable nuclear antigen (ENA) antibody-positive

and antineutrophil cytoplasmic antibody (ANCA)-positive

to analyze prognostic differences. The Kaplan-Meier survival curve was used to calculate median survival time

and Cox regression analysis was performed to evaluate prognostic factors.

Results

A total of 189 patients with MM were included

with 57 (30.16%) in the PA group and 132 (69.84%) in the NA group. All patients received treatment; 58 (30.69%) received anti-CD38 monoclonal antibody therapy

and 57 (30.16%) underwent auto-HSCT. After induction therapy

the ORR was 75.66% (143/189)

comprising a PR in 43.39% (82/189) and a CR in 32.28% (61/189). The CR rate was significantly lower in the PA group than in the NA group (21.05%

37.12%

=0.031). At a median follow-up of 39 months (IQR 16 to 59)

the median progression-free survival (PFS) was 37 months (IQR 16 to 58) for the enti

re cohort

while the median overall survival (OS) was not reached. Kaplan-Meier analysis showed significantly shorter median PFS in the PA group versus the NA group (31

43 months

=0.048). Subgroup analysis based on specific autoantibodies revealed that patients with anti-ENA antibody positivity had significantly shorter median OS (41

61 months

=0.038) and PFS (28

41 months

=0.001) than those without. No significant differences in OS or PFS were observed between ANA/ANCA-positive and -negative groups. Cox regression identified anti-ENA antibody positivity (

=0.004) and male sex (

0.001) as independent risk factors for OS

whereas achievement of CR post-induction (

=0.002) and anti-CD38 therapy (

=0.008) were protective factors. For PFS

independent risk factors were male sex (

0.001) and anti-ENA positivity (

0.001)

with protective factors including elevated fibrinogen (

=0.011)

achievement of CR (

=0.009)

and anti-CD38 therapy (

=0.011).

Conclusion

MM patients with positive autoantibodies exhibit inferior responses to induction therapy and poor long-term outcomes. Anti-ENA antibody positivity is an independent risk factor for both OS and PFS in MM.

关键词

Keywords

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