Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab
Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab
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DOI：
10.1016/j.jdermsci.2017.07.007
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发表时间：
2017-11-01
影响因子：
4.6
通讯作者：
Matsushita, Shigeto
中科院分区：
文献类型：
--
作者：
Fujisawa, Yasuhiro;Yoshino, Koji;Matsushita, Shigeto
背景：虽然纳武单抗可显着延长转移性黑色素瘤的生存期，但约 10% 的患者会经历严重甚至致命的免疫相关不良事件 (irAE)。因此，预测 irAE 的生物标志物引起了极大的兴趣。 目的：我们旨在将常规血细胞计数参数的变化与接受纳武单抗治疗的黑色素瘤患者中严重 irAE（3/4 级 [G3/4] 或肺/胃肠道 [肺/胃肠道] irAE）的发生相关联。方法：我们回顾性分析了来自日本 8 个机构的 101 名接受纳武单抗治疗的黑色素瘤患者的数据。我们使用逻辑回归分析来研究严重 irAE 与治疗期间常规血细胞计数参数（总白细胞 [WBC] 计数、相对中性粒细胞、单核细胞、淋巴细胞和嗜酸性粒细胞计数）波动之间的关联。使用受试者工作特征曲线来确定血细胞计数参数和曲线下面积 (AUC) 的截止值。结果：单变量分析显示，G3/4 irAE 与白细胞总数增加（P = 0.034，截止值 = +27%，AUC= 0.68，比值比 [OR] = 1.58）和相对淋巴细胞计数减少（RLC，P = 0.042，截止值）相关。 = -23%，AUC= 0.65，OR= 1.65）。然而，多变量分析显示，相同的因素，白细胞计数增加（P = 0.014，截止值 = +59.1%，AUC = 0.79，OR = 6.04）和 RLC 减少（P = 0.012，截止值 = 32.3%，AUC = 0.81，OR = 5.01）是与肺/胃肠道 irAE 相关的独立因素。结论：我们的结果表明WBC 计数增加和 RLC 减少与 G3/4 和肺/胃肠道 irAE 相关。我们的分析基于注意到 irAE 发生的数据点，因此，这些因素不能预测，但它们可能是接受纳武单抗治疗的黑色素瘤患者发生严重 irAE 的“信号”。 (C) 2017 年日本皮肤病研究学会。由爱思唯尔爱尔兰有限公司出版。保留所有权利。
Background: Although nivolumab significantly prolongs survival of metastatic melanoma, about 10% of patients experience severe, even fatal immune-related adverse events (irAEs). Biomarkers to predict irAEs are, therefore, of great interest.Objective: We aimed to correlate changes in routine blood count parameters to the occurrence of serious irAEs (grade 3/4 [G3/4] or lung/gastrointestinal [lung/GI] irAEs) in patients with melanoma who were treated with nivolumab.Methods: We retrospectively analyzed data from 101 patient with melanoma treated with nivolumab from 8 institutes in Japan. We used logistic regression analyses to investigate associations between severe irAEs and fluctuations in routine blood count parameters (total white blood cell [WBC] count, relative neutrophil, monocyte, lymphocyte, and eosinophil count) during the treatment. Receiver operating characteristic curve was used to determine a cutoff value for the blood count parameters and area under the curve (AUC).Results: Univariate analysis revealed that G3/4 irAEs were associated with increased total WBC count (P = 0.034, cutoff value = +27%, AUC= 0.68, odds ratio [OR] = 1.58) and decreased relative lymphocyte count (RLC, P= 0.042, cutoff value = -23%, AUC= 0.65, OR= 1.65). However, multivariate analysis showed that the same factors, increased WBC count (P = 0.014, cutoff value = +59.1%, AUC = 0.79, OR= 6.04) and decreased RLC (P = 0.012, cutoff value = 32.3%, AUC= 0.81, OR= 5.01) were independent factors associated with lung/GI irAEs.Conclusions: Our results suggest that increased WBC count and decreased RLC are associated with G3/4 and lung/GI irAEs. Our analysis was based on the data point at which irAE occurrence was noticed and, therefore, these factors are not predictive, however, they could be a "signal" of severe irAE occurrence in patients with melanoma treated with nivolumab. (C) 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.