Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana 1230, Boston, MA, 02215, USA.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
J Immunother Cancer. 2018 Jan 22;6(1):5. doi: 10.1186/s40425-018-0315-0.
An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in several malignancies. However, its role with contemporary immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB.
We examined NLR at baseline and 6 (±2) weeks later in 142 patients treated between 2009 and 2017 at Dana-Farber Cancer Institute (Boston, USA). Landmark analysis at 6 weeks was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Cox and logistic regression models allowed for adjustment of line of therapy, number of IMDC risk factors, histology and baseline NLR.
Median follow up was 16.6 months (range: 0.7-67.8). Median duration on therapy was 5.1 months (<1-61.4). IMDC risk groups were: 18% favorable, 60% intermediate, 23% poor-risk. Forty-four percent were on first-line ICB and 56% on 2nd line or more. Median NLR was 3.9 (1.3-42.4) at baseline and 4.1 (1.1-96.4) at week 6. Patients with a higher baseline NLR showed a trend toward lower ORR, shorter PFS, and shorter OS. Higher NLR at 6 weeks was a significantly stronger predictor of all three outcomes than baseline NLR. Relative NLR change by ≥25% from baseline to 6 weeks after ICB therapy was associated with reduced ORR and an independent prognostic factor for PFS (p < 0.001) and OS (p = 0.004), whereas a decrease in NLR by ≥25% was associated with improved outcomes.
Early decline and NLR at 6 weeks are associated with significantly improved outcomes in mRCC patients treated with ICB. The prognostic value of the readily-available NLR warrants larger, prospective validation.
中性粒细胞与淋巴细胞比值（NLR）升高与多种恶性肿瘤的预后不良相关。然而，其在当代免疫检查点阻断（ICB）中的作用尚不清楚。我们研究了 NLR 在接受 PD-1/PD-L1 ICB 治疗的转移性肾细胞癌（mRCC）患者中的作用。
我们在 2009 年至 2017 年期间在达纳-法伯癌症研究所（美国波士顿）接受治疗的 142 名患者中检查了基线和 6（±2）周时的 NLR。进行 6 周的里程碑分析，以探讨相对 NLR 变化对总生存期（OS）、无进展生存期（PFS）和客观缓解率（ORR）的预后价值。Cox 和逻辑回归模型允许调整治疗线、IMDC 风险因素的数量、组织学和基线 NLR。
中位随访时间为 16.6 个月（范围：0.7-67.8）。中位治疗时间为 5.1 个月（<1-61.4）。IMDC 风险组为：18%为低危，60%为中危，23%为高危。44%的患者接受一线 ICB，56%的患者接受二线或以上治疗。基线时 NLR 中位数为 3.9（1.3-42.4），第 6 周时 NLR 中位数为 4.1（1.1-96.4）。基线 NLR 较高的患者的 ORR 较低，PFS 和 OS 较短。6 周时 NLR 升高是所有三个结局的更强预测因子，优于基线 NLR。与 ICB 治疗后第 6 周 NLR 基线相比，相对 NLR 变化≥25%与降低的 ORR 相关，是 PFS（p<0.001）和 OS（p=0.004）的独立预后因素，而 NLR 下降≥25%与改善结局相关。
在接受 ICB 治疗的 mRCC 患者中，早期下降和第 6 周时 NLR 与显著改善的结局相关。易于获得的 NLR 的预后价值需要更大的前瞻性验证。
