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中性粒细胞与嗜酸性粒细胞比值作为抗 PD-1 治疗晚期黑色素瘤患者临床结局的生物标志物。

Neutrophil-to-eosinophil ratio as a biomarker for clinical outcomes in advanced stage melanoma patients treated with anti-PD-1 therapy.

机构信息

University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, USA.

Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, USA.

出版信息

Pigment Cell Melanoma Res. 2023 Nov;36(6):501-511. doi: 10.1111/pcmr.13109. Epub 2023 Jul 7.

Abstract

Neutrophil-to-lymphocyte ratios (NLR) and eosinophil counts are associated with improved survival in melanoma patients treated with immune checkpoint inhibitors, but no study has investigated neutrophil-to-eosinophil ratios (NER) as a predictive indicator in this population. In this retrospective study evaluating anti-PD-1 treated patients with advanced melanoma, progression-free survival (PFS), overall survival (OS), objective response rates (ORR), and risk of high-grade (grade ≥3) immune-related adverse events (irAEs) were compared between groups defined by median pretreatment NLR and NER as well as median NLR and NER at 1-month post-treatment. Lower baseline NLR and NER were associated with improved OS [HR: 0.504, 95% CI: 0.328-0.773, p = .002 and HR: 0.442, 95% CI: 0.288-0.681, p < .001, respectively] on univariate testing. After accounting for multiple covariates, our multivariate analysis found that lower pretreatment NER was associated with better ORR (by irRECIST) (OR: 2.199, 95% CI: 1.071-4.582, p = .033) and improved OS (HR: 0.480, 95% CI: 0.296-0.777, p = .003). Baseline NLR, 1-month NLR, and 1-month NER were not associated with ORR, PFS, or OS outcomes; but 1-month NER correlated with lower risk of grade ≥3 irAEs (OR: 0.392, 95% CI: 0.165-0.895, p = .029). Our findings suggest baseline NER merits additional investigation as a novel prognostic marker for advanced melanoma patients receiving anti-PD-1-based regimens.

摘要

中性粒细胞与淋巴细胞比值(NLR)和嗜酸性粒细胞计数与接受免疫检查点抑制剂治疗的黑色素瘤患者的生存改善相关,但尚无研究调查中性粒细胞与嗜酸性粒细胞比值(NER)作为该人群的预测指标。在这项评估抗 PD-1 治疗的晚期黑色素瘤患者的回顾性研究中,比较了根据治疗前 NLR 和 NER 中位数以及治疗后 1 个月 NLR 和 NER 中位数定义的两组患者的无进展生存期(PFS)、总生存期(OS)、客观缓解率(ORR)和发生高级别(≥3 级)免疫相关不良事件(irAE)的风险。在单变量检验中,较低的基线 NLR 和 NER 与 OS 改善相关[风险比(HR):0.504,95%置信区间(CI):0.328-0.773,p=0.002 和 HR:0.442,95%CI:0.288-0.681,p<0.001]。在考虑多个协变量后,我们的多变量分析发现,较低的治疗前 NER 与更好的 ORR(根据 irRECIST)相关(比值比(OR):2.199,95%CI:1.071-4.582,p=0.033)和 OS 改善(HR:0.480,95%CI:0.296-0.777,p=0.003)。基线 NLR、1 个月 NLR 和 1 个月 NER 与 ORR、PFS 或 OS 结果无关;但 1 个月 NER 与发生≥3 级 irAE 的风险降低相关(OR:0.392,95%CI:0.165-0.895,p=0.029)。我们的研究结果表明,基线 NER 值得进一步研究,作为接受抗 PD-1 方案治疗的晚期黑色素瘤患者的新型预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/410f/11851330/38c6ed453d49/nihms-2058056-f0001.jpg

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