Department of Immunobiology, Yale University School of Medicine, New Haven, USA.
Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
Ann Oncol. 2017 Aug 1;28(8):1988-1995. doi: 10.1093/annonc/mdx190.
Surrogate biomarkers of efficacy are needed for anti-PD1/PD-L1 therapy, given the existence of delayed responses and pseudo-progressions. We evaluated changes in serum IL-8 levels as a biomarker of response to anti-PD-1 blockade in melanoma and non-small-cell lung cancer (NSCLC) patients.
Metastatic melanoma and NSCLC patients treated with nivolumab or pembrolizumab alone or nivolumab plus ipilimumab were studied. Serum was collected at baseline; at 2-4 weeks after the first dose; and at the time-points of response evaluation. Serum IL-8 levels were determined by sandwich ELISA. Changes in serum IL-8 levels were compared with the Wilcoxon test and their strength of association with response was assessed with the Mann-Whitney test. Accuracy of changes in IL-8 levels to predict response was estimated using receiver operation characteristics curves.
Twenty-nine melanoma patients treated with nivolumab or pembrolizumab were studied. In responding patients, serum IL-8 levels significantly decreased between baseline and best response (P <0.001), and significantly increased upon progression (P = 0.004). In non-responders, IL-8 levels significantly increased between baseline and progression (P = 0.013). Early changes in serum IL-8 levels (2-4 weeks after treatment initiation) were strongly associated with response (P <0.001). These observations were validated in 19 NSCLC patients treated with nivolumab or pembrolizumab (P = 0.001), and in 15 melanoma patients treated with nivolumab plus ipilimumab (P <0.001). Early decreases in serum IL-8 levels were associated with longer overall survival in melanoma (P = 0.001) and NSCLC (P = 0.015) patients. Serum IL-8 levels also correctly reflected true response in three cancer patients presenting pseudoprogression.
Changes in serum IL-8 levels could be used to monitor and predict clinical benefit from immune checkpoint blockade in melanoma and NSCLC patients.
鉴于抗 PD1/PD-L1 治疗存在延迟反应和假性进展，因此需要有效的替代生物标志物。我们评估了血清 IL-8 水平的变化作为抗 PD-1 阻断在黑色素瘤和非小细胞肺癌（NSCLC）患者中的反应生物标志物。
研究了单独使用纳武单抗或派姆单抗或纳武单抗联合伊匹单抗治疗的转移性黑色素瘤和 NSCLC 患者。在基线时、首次剂量后 2-4 周以及反应评估时采集血清。通过夹心 ELISA 测定血清 IL-8 水平。使用 Wilcoxon 检验比较血清 IL-8 水平的变化，并使用 Mann-Whitney 检验评估其与反应的关联强度。使用接收者操作特征曲线估计 IL-8 水平变化预测反应的准确性。
研究了 29 例接受纳武单抗或派姆单抗治疗的黑色素瘤患者。在有反应的患者中，血清 IL-8 水平在基线和最佳反应时显著降低（P<0.001），在进展时显著升高（P=0.004）。在无反应者中，IL-8 水平在基线和进展时显著升高（P=0.013）。治疗开始后 2-4 周的血清 IL-8 水平早期变化与反应强烈相关（P<0.001）。这些观察结果在接受纳武单抗或派姆单抗治疗的 19 例 NSCLC 患者（P=0.001）和接受纳武单抗联合伊匹单抗治疗的 15 例黑色素瘤患者（P<0.001）中得到验证。黑色素瘤（P=0.001）和 NSCLC（P=0.015）患者中血清 IL-8 水平的早期降低与总生存期延长相关。血清 IL-8 水平也正确反映了 3 例出现假性进展的癌症患者的真实反应。
血清 IL-8 水平的变化可用于监测和预测黑色素瘤和 NSCLC 患者免疫检查点阻断的临床获益。
