Lymphocyte counts independently predict overall survival in advanced cancer patients: A biomarker for IL-2 immunotherapy
Lymphocyte counts independently predict overall survival in advanced cancer patients: A biomarker for IL-2 immunotherapy
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DOI：
10.1097/00002371-200309000-00002
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发表时间：
2003-09-01
影响因子：
3.9
通讯作者：
Nespoli, A
中科院分区：
文献类型：
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作者：
Fumagalli, LA;Vinke, J;Nespoli, A
白介素2(IL-2)以携带IL-2受体的细胞为靶标，诱导不同程度的淋巴细胞增多症。这项研究回顾评估了淋巴细胞增多，除了基线的临床特征和肿瘤的客观反应外，是否可以预测接受IL-2皮下注射的转移性肾癌患者的总生存率。266例晚期肾癌患者的总存活率、临床特征、肿瘤反应和在基线和第一个治疗周期中的总淋巴细胞计数，采用4种不同一线方案中的1种进行治疗。以IL-2为基础的方案，采用COX多因素分析进行研究。7+/-5.9周IL-2累积剂量和治疗时间(+/-SD)的中位数分别为232+/-282×10(6)/m(2)。中位总生存期(OS)为13.1个月(0.7~86.9+)。肿瘤预后：CR 9例(3%)(OS=NR)；PR 35例(13%)(OS=19.7个月)；SD 117例(44%)(OS=15.1个月)；PD 105例(39%)(OS=6.4个月)。淋巴细胞计数的中位数在基线(25-75,900-1900/mm(3))时为1400/mm(3)，最大值(25-75,2600-4800/mm(3))为3600/mm(3)。在校正了临床特征(PS ECOG 0与大于或等于1，从初次诊断开始的时间大于或等于1)和肿瘤反应(CR，PR)后，每1000个淋巴细胞/毫米(3)的死亡风险显著降低11%(RR 0.89；95%CI 0.82-0.97)。两步自举过程证实了这种预测性能。淋巴细胞计数监测是宿主对皮下IL-2治疗反应的生物标志物，可用于多模式临床评估，因为它独立于肿瘤反应和主要临床特征预测晚期癌症患者的总体生存。
Interleukin-2 (IL-2) targets cells bearing IL-2 receptors and induces different degrees of lymphocytosis. This study retrospectively evaluated whether lymphocytosis, in addition to clinical characteristics at baseline and to tumor objective response, may predict overall survival in metastatic renal cell carcinoma patients who received IL-2 subcutaneously (s.c.). Overall survival, clinical characteristics, tumor response, and total lymphocyte count at baseline and during the first treatment cycle of 266 advanced renal cell cancer patients, treated with 1 of 4 different first-line s.c. IL-2-based protocols, were studied using the Cox multivariate analysis. Median IL-2 cumulative dose and length of treatment (+/-SD) were 232 +/- 282 x 10(6)/m(2) in 7 +/- 5.9 weeks, respectively. Median overall survival (os) was 13.1 months (range 0.7-86.9+) in all. Tumor outcome consisted of: 9 CR (3%) (os = NR); 35 PR (13%) (os = 19.7 months.); 117 SD (44%) (os = 15.1 months); 105 PD (39%) (os = 6.4 months). Median lymphocyte counts were 1400/mm(3) at baseline (25th-75th, 900-1900/mm(3)) and 3600/mm(3) as a maximum value (25th-75th, 2600-4800/mm(3)). Death risk significantly decreased by 11% for each 1,000 lymphocytes/mm(3) (RR 0.89; 95% CI 0.82-0.97), after correcting for clinical characteristics (PS ECOG 0 versus greater than or equal to1, time from primary diagnosis greater than or equal to2 years versus 1) and tumor response (CR, PR). A two-step bootstrapping procedure confirmed such predictive performance. Lymphocyte count monitoring represents a biomarker of the host response to subcutaneous IL-2 treatment useful for multimodal clinical assessment, as it predicts overall survival in advanced cancer patients independently from tumor response and from main clinical characteristics.