在开始使用伊匹木单抗治疗前测得的高中性粒细胞与淋巴细胞比值与黑色素瘤患者的总生存期缩短有关。
High neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall survival in patients with melanoma.
作者信息
Zaragoza J, Caille A, Beneton N, Bens G, Christiann F, Maillard H, Machet L
机构信息
Department of Dermatology, Centre Hospitalier Régional et Universitaire (CHRU) de Tours, Tours, 37044, France.
Inserm Centre d'Investigation Clinique (CIC) 1415, Centre Hospitalier Régional et Universitaire (CHRU) de Tours, Tours, 37044, France.
出版信息
Br J Dermatol. 2016 Jan;174(1):146-51. doi: 10.1111/bjd.14155. Epub 2015 Nov 25.
BACKGROUND
There is an unmet need to identify markers predictive of response to ipilimumab in patients with melanoma because the number of responders to ipilimumab is low and its cost is very high. An increase in absolute lymphocyte count (ALC) or low neutrophil/lymphocyte ratio (NLR) just before the third infusion has been reported to be associated with better overall survival (OS).
OBJECTIVES
Our aim was to determine whether NLR measured before the first infusion was associated with OS.
PATIENTS AND METHODS
Data were collected on a consecutive series of 58 patients treated with ipilimumab in four hospitals, including 51 at stage M1c and four at stage M1b. The influences of the NLR and other factors such as lactate dehydrogenase (LDH), performance status, ALC, absolute neutrophil count (ANC) and corticosteroids on survival were studied. We also assessed this association with NLR categorized as a binary variable. The cut-off value for the NLR was determined with time-dependent receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using Cox regression models.
RESULTS
High NLR (≥) 4, high ANC LDH levels (>2), performance status ≥2, symptomatic brain metastases, and corticosteroids before week 1 were associated with poorer survival on univariate analysis. Using multivariate analysis, a significant association between high NLR (continuous variable) and poorer survival was demonstrated and remained significant after adjustment on potential confounders [hazard ratio (HR) = 1·21, 95% confidence interval (CI) 1·07-1·36]. NLR ≥4 was an independent prognostic factor (HR = 2·2, 95% CI 1·01-4·78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1·28, 95% CI 0·54-3·06).
CONCLUSIONS
High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.
背景
由于接受伊匹单抗治疗的黑色素瘤患者中，有反应者数量较少且费用高昂，因此迫切需要确定可预测伊匹单抗疗效的标志物。据报道，在第三次输注前绝对淋巴细胞计数（ALC）增加或中性粒细胞/淋巴细胞比值（NLR）较低与更好的总生存期（OS）相关。
目的
我们的目的是确定首次输注前测量的NLR是否与OS相关。
患者和方法
收集了四家医院连续58例接受伊匹单抗治疗患者的数据，其中51例为M1c期，4例为M1b期。研究了NLR以及其他因素（如乳酸脱氢酶（LDH）、体能状态、ALC、绝对中性粒细胞计数（ANC）和皮质类固醇）对生存的影响。我们还将NLR作为二元变量评估了这种关联。通过时间依赖性受试者工作特征（ROC）分析确定NLR的临界值。使用Cox回归模型进行单因素和多因素分析。
结果
单因素分析显示，高NLR（≥4）、高ANC、LDH水平（>2）、体能状态≥2、有症状的脑转移以及第1周前使用皮质类固醇与较差的生存率相关。使用多因素分析，高NLR（连续变量）与较差的生存率之间存在显著关联，在对潜在混杂因素进行调整后仍具有显著性[风险比（HR）=1.21，95%置信区间（CI）1.07-1.36]。NLR≥4是一个独立的预后因素（HR=2.2，95%CI 1.01-4.78）。第1周前使用皮质类固醇不是一个独立的预后因素（HR=1.28，95%CI 0.54-3.06）。
结论
转移性黑色素瘤患者在开始伊匹单抗治疗前高NLR（≥4）是生存不良的独立预后指标。
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