Effects of anti-drug antibody on clinical efficacy and adverse reactions of immunotherapy for non-small cell lung cancer

Xianlan ZHAO; Jixi LI; Qiao YANG; Shixun LI; Yongxin YU; Feng LI; Mengxia LI; Jianguo SUN

doi:10.16016/j.1000-5404.202103060

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Effects of anti-drug antibody on clinical efficacy and adverse reactions of immunotherapy for non-small cell lung cancer

更新时间：2026-01-09

- Effects of anti-drug antibody on clinical efficacy and adverse reactions of immunotherapy for non-small cell lung cancer
- Journal of Third Military Medical University Vol. 43, Issue 17, Pages: 1673-1678(2021)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the Clinical Fund of Army Medical University(2018XLC1010);the Chongqing Excellent Talent Training Program(cstccxljrc201910)
- DOI：10.16016/j.1000-5404.202103060
  CLC：
- Received：06 March 2021，
  
  Published：15 September 2021
- 稿件说明：
移动端阅览
Xianlan ZHAO, Jixi LI, Qiao YANG, et al. Effects of anti-drug antibody on clinical efficacy and adverse reactions of immunotherapy for non-small cell lung cancer[J]. Journal of Third Military Medical University, 2021, 43(17): 1673-1678.
DOI：

Xianlan ZHAO, Jixi LI, Qiao YANG, et al. Effects of anti-drug antibody on clinical efficacy and adverse reactions of immunotherapy for non-small cell lung cancer[J]. Journal of Third Military Medical University, 2021, 43(17): 1673-1678. DOI： 10.16016/j.1000-5404.202103060.

摘要

目的

探索非小细胞肺癌(non-small cell lung cancer

NSCLC)患者接受免疫检查点抑制剂(immune checkpoint inhibitors

ICIs)治疗后产生的抗药物抗体(anti-drug antibody，ADA)对患者临床疗效及不良反应的影响。

方法

从陆军军医大学第二附属医院及陆军特色医疗中心收集2016年4月至2019年9月使用帕博利珠单抗或纳武利尤单抗的Ⅲ/Ⅳ期NSCLC患者共26例，在首次输注后2个月左右采集血样，使用酶联免疫法检测血浆中ADA水平，并分析ADA对ICIs的临床疗效、疾病进展及免疫相关不良反应(immune-related adverse events

irAEs)的影响。

结果

12例接受纳武利尤单抗治疗的患者，ADA检测结果均为阴性，最佳总体反应率(best overall response

bOR)为25.0%，中位无进展生存期(median progression-free survival

mPFS)为4.1(1.9~26.9)个月，中位总生存期(median overall survival

mOS)为12.4个(4.8~26.9)月。14例接受帕博利珠单抗治疗的患者，bOR为50.0%，mPFS为10.9(2.2~15.3)个月，mOS为19.0(3.5~29.6)个月；其中3例ADA阳性，11例ADA阴性，ADA阳性患者的mPFS(9.9

12.4个月，

=0.280)、mOS(19.0

29.6个月，

=0.874)以及采血后至出现影像进展的中位时间(7.5

8.6个月，

=0.365)均短于ADA阴性患者；ADA阳性和阴性患者2级以上irAEs的发生率分别为66.7%和23.7%。

结论

ADA监测对于接受ICIs治疗的NSCLC患者有一定临床价值。帕博利珠单抗ADA阳性患者生存时间较短，但ADA状态对其bOR和irAEs的影响不显著。

Abstract

Objective

To explore the effects of anti-drug antibody (ADA) on clinical efficacy and adverse reactions in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).

Methods

A total of 26 patients with stage Ⅲ/Ⅳ NSCLC undergoing pembrolizumab or nivolumab treatment from April 2016 to September 2019 were collected from the Second Affiliated Hospital and Daping Hospital of Army Medical University. Blood samples were collected about 2 months after the first infusion of ICIs. The level of ADA in plasma were measured by enzyme-linked immunosorbent assay. The effects of ADA on the clinical efficacy

disease progression and immune-related adverse events (irAEs) of ICIs were analyzed.

Results

In 12 patients treated with nivolumab

the results of ADA test were negative

the best overall response rate (bOR) was 25.0%

the median progression-free survival (mPFS) was 4.1(1.9~26.9) months

and the median overall survival (mOS) was 12.4 (4.8~26.9) months. In 14 patients treated with pembrolizumab

bOR was 50.0%

mPFS was 10.9 (2.2~25.3) months

and mOS was 19.0 (5.2~29.6) months; 3 of 14 patients were ADA-positive

11 were ADA-negative. mPFS (9.9

12.4 months

=0.280)

mOS (19.0

29.6 months

=0.874) and median time to radiographic progression after blood sampling (7.5

8.6 months

=0.365) were significantly shorter in the ADA-positive patients than the ADA-negative patients. irAEs occurred in 2 (66.7%) ADA positive patients and 3 (27.3%) ADA negative patients.

Conclusion

ADA monitoring in NSCLC patients has certain clinical value for the treatment of ICIs

and ADA positive of pembrolizumab has an effect on the shorter survival time of patients. However

the effect of ADA status is not significant on bOR and irAEs.

关键词

Keywords

references

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