A transient increase in eosinophils is associated with prolonged survival in men with metastatic castration-resistant prostate cancer who receive sipuleucel-T.
A transient increase in eosinophils is associated with prolonged survival in men with metastatic castration-resistant prostate cancer who receive sipuleucel-T.
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DOI：
10.1158/2326-6066.cir-14-0073
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发表时间：
2014-10
影响因子：
10.1
通讯作者：
Dreicer R
中科院分区：
文献类型：
--
作者：
McNeel DG;Gardner TA;Higano CS;Kantoff PW;Small EJ;Wener MH;Sims RB;DeVries T;Sheikh NA;Dreicer R
SiPuleucel-T是一种自体细胞免疫疗法，用于治疗无症状或无症状的转移性去势耐受前列腺癌(MCRPC)。化疗常用的传统短期临床疗效指标与接受西普鲁尔-T治疗的患者的生存率没有相关性。这项回溯性研究旨在评估实验室参数作为可能的早期生物标记物与西普鲁尔-T治疗后的临床益处相关。在mCRPC的3个随机对照III期临床试验中，接受西普鲁塞-T治疗的患者包括：IMPACT(NCT00065442，n=512)、D9901(NCT00005947，n=127)和D9902A(NCT01133704，n=98)。如果这些试验的患者的样本由中心实验室分析，并且可以从基线和≥1治疗后时间点获得数据，则纳入这项研究(n=377)。我们发现，西普鲁尔-T治疗与血清嗜酸性粒细胞计数在第6周的一过性增加有关，在第14周，28%的患者(105/377)的嗜酸性粒细胞计数在14周时消失。嗜酸性粒细胞的增加与诱导免疫反应、前列腺癌特异性生存期延长(HR=0.713；95%可信区间0.525-0.970；P=0.031)和总体生存趋势有关(HR=0.753；95%CI，0.563-1.008；P=0.057)。血清球蛋白中值水平也有一过性升高，这与抗原特异性抗体反应有关；然而，这与较长的生存期无关。我们的结论是，在第6周，嗜酸性粒细胞的一过性增加可能是一个有用的、客观的、短期的指标，可以用来评估mCRPC患者使用siPuleucel-T后的全球免疫激活和生存益处。这一观察结果值得在未来的临床试验中进行前瞻性评估。
Sipuleucel-T is an autologous cellular immunotherapy used to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Traditional short-term indicators of clinical response commonly used with chemotherapy have not correlated with survival in patients treated with sipuleucel-T. This retrospective study aimed to evaluate laboratory parameters as possible early biomarkers associated with clinical benefit following sipuleucel-T treatment. Patients treated with sipuleucel-T from 3 randomized, controlled, phase III clinical trials in mCRPC were considered: IMPACT (NCT00065442, n = 512), D9901 (NCT00005947, n = 127), and D9902A (NCT01133704, n = 98). Patients from these trials were included in this study if their samples were analyzed by the central laboratory, and if data were available from baseline and ≥1 post-treatment time point (n = 377). We found that sipuleucel-T treatment was associated with a transient increase in serum eosinophil count at week 6 that resolved by week 14 in 28% of patients (105/377). This eosinophil increase correlated with induced immune response, longer prostate cancer-specific survival (HR = 0.713; 95% confidence interval [CI], 0.525–0.970; P = 0.031) and trend in overall survival (HR = 0.753; 95% CI, 0.563–1.008; P = 0.057). Median serum globulin protein levels also increased transiently, which was associated with antigen-specific antibody responses; however, this did not correlate with longer survival. We conclude that transient increases in eosinophils at week 6 may be a useful, objective, short-term indicator of global immune activation and survival benefit with sipuleucel-T in patients with mCRPC. This observation warrants prospective evaluation in future clinical trials.