Pretreatment Eosinophil Counts in Patients With Advanced or Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1 Checkpoint Inhibitors.
Pretreatment Eosinophil Counts in Patients With Advanced or Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1 Checkpoint Inhibitors.
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DOI：
10.1097/cji.0000000000000372
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发表时间：
2021-09-01
期刊：
影响因子：
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通讯作者：
Rosenberg JE
中科院分区：
文献类型：
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作者：
Mota JM;Teo MY;Whiting K;Li HA;Regazzi AM;Lee CH;Funt SA;Bajorin D;Ostrovnaya I;Iyer G;Rosenberg JE
嗜酸性粒细胞影响抗肿瘤免疫，并可能预测对免疫检查点抑制剂（ICI）治疗的反应。为了检查血液嗜酸性粒细胞计数与接受ICI治疗的晚期或转移性尿路上皮癌（mUC）患者结局之间的相关性，我们确定了两个ICI治疗队列：发现（n=60）和验证（n=111）。化疗队列用作对照（一线含铂化疗，n=75;二线或更高剂量培美曲塞，n=77）。主要终点为总生存期（OS）。次要终点是治疗时间（ToT）和无进展生存期。采用考克斯比例风险模型进行单变量和多变量分析。使用界标分析分析ICI治疗开始后第2/3周和第6周嗜酸性粒细胞计数变化之间的相关性。ICI队列的基线特征相似。在发现队列中，确定了治疗前嗜酸性粒细胞计数的最佳截止值（Eos-Lo：<100个细胞/μL; n=9 [15%]; Eos-Hi：≥100个细胞/μL; n=51 [85%]）。Eos-Lo与较差结局相关（OS：HR，3.98 [95% CI，1.85-8.56]; P<0.013; ToT：HR，2.45 [95% CI，1.17-5.10]; P=0.017）。这在验证队列中得到证实（Eos-Lo：n=17 [15%]; Eos-Hi：n=94 [85%]）（OS：HR，2.51 [95% CI，1.31-4.80]; P=0.006; ToT：HR，2.22 [95% CI，1.29-3.80]; P=0.004），在调整其他预后因素后仍具有显著性。第2/3周和第6周嗜酸性粒细胞计数的变化与结局无明显相关性。在化疗队列中，嗜酸性粒细胞计数与结果无关。总之，治疗前嗜酸性粒细胞计数低与接受ICI治疗的mUC患者的预后较差相关，并且可能代表一种新的预测生物标志物。
Eosinophils influence antitumor immunity and may predict response to treatment with immune checkpoint inhibitors (ICIs). To examine the association between blood eosinophil counts and outcomes in patients with advanced or metastatic urothelial carcinoma (mUC) treated with ICIs, we identified two ICI-treated cohorts: discovery (n=60) and validation (n=111). Chemotherapy cohorts were used as comparators (first-line platinum-based chemotherapy, n=75; second-line or more pemetrexed, n=77). The primary endpoint was overall survival (OS). Secondary endpoints were time on treatment (ToT) and progression-free survival. Univariate and multivariate analyses were performed using Cox proportional hazard models. Associations between changes in eosinophil count at weeks 2/3 and 6 after the start of ICI treatment were analyzed using landmark analyses. Baseline characteristics of the ICI cohorts were similar. In the discovery cohort, an optimal cutoff for pretreatment eosinophil count was determined (Eos-Lo: <100 cells/μL; n=9 [15%]; Eos-Hi: ≥100 cells/μL; n=51 [85%]). Eos-Lo was associated with inferior outcomes (OS: HR, 3.98 [95% CI, 1.85–8.56]; P<0.013; ToT: HR, 2.45 [95% CI, 1.17–5.10]; P=0.017). This was confirmed in the validation cohort (Eos-Lo: n=17 [15%]; Eos-Hi: n=94 [85%]) (OS: HR, 2.51 [95% CI, 1.31–4.80]; P=0.006; ToT: HR, 2.22 [95% CI, 1.29–3.80]; P=0.004), and remained significant after adjustment for other prognostic factors. Changes in eosinophil counts at weeks 2/3 and 6 were not clearly associated with outcomes. In chemotherapy cohorts, eosinophil counts were not associated with outcomes. In conclusion, low pretreatment eosinophil count was associated with poorer outcomes in patients with mUC treated with ICIs, and may represent a new predictive biomarker.