Impacts of cachexia progression in addition to serum IgG and blood lymphocytes on serum nivolumab in advanced cancer patients
Impacts of cachexia progression in addition to serum IgG and blood lymphocytes on serum nivolumab in advanced cancer patients
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DOI：
10.1007/s00228-021-03199-6
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发表时间：
2021-08-19
影响因子：
2.9
通讯作者：
Kawakami, Junichi
中科院分区：
文献类型：
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作者：
Abe, Kazuki;Shibata, Kaito;Kawakami, Junichi
目的癌症患者血清纳武单抗浓度变化较大。癌症恶病质诱导全身性炎症促进内源性蛋白质的消除，而其与血清纳武单抗的关联仍不清楚。本研究旨在评估恶病质进展以及血液成分对癌症患者血清纳武利尤单抗的影响。方法38例非小细胞肺癌或肾细胞癌患者接受每两周一次的纳武利尤单抗静脉给药。在第7次纳武单抗给药或之后给药前采集血样。测定血清纳武单抗以及血清蛋白、炎症标志物和外周血白细胞。使用格拉斯哥预后评分（GPS）对癌症恶病质进行分类。在研究期间监测免疫相关不良事件（irAE）。结果癌症患者的血清纳武单抗浓度变化很大（四分位距，12-21 μ g/mL/mg/kg）。血清纳武利尤单抗浓度与血清白蛋白呈正相关，与血清球蛋白和免疫球蛋白G（IgG）呈负相关。血清纳武单抗和血液淋巴细胞之间观察到负相关。关于恶病质进展，与GPS 0或1的患者相比，GPS 2的患者具有更高的血清白细胞介素-6浓度和更低的血清纳武单抗浓度。GPS、血清IgG和血液淋巴细胞被确定为血清纳武单抗的自变量。irAE的发生率与nivolumab剂量或血清nivolumab无关。结论恶病质进展对癌症患者血清nivolumab水平有负面影响。血清纳武利尤单抗的个体间差异的特征在于恶病质进展以及血液成分。
Purpose Serum nivolumab concentrations exhibit a large variation in cancer patients. Cancer cachexia inducing systemic inflammation promotes the elimination of endogenous proteins, while its association with serum nivolumab remains unclear. The present study aimed to evaluate the impacts of cachexia progression in addition to blood components on serum nivolumab in cancer patients. Methods Thirty-eight non-small-cell lung cancer or renal cell cancer patients receiving biweekly intravenous nivolumab were enrolled. Blood samples were collected just before dosing at the 7th administration of nivolumab or later. Serum nivolumab together with serum proteins, inflammatory markers, and peripheral blood leukocytes were determined. Cancer cachexia was classified using the Glasgow Prognostic Score (GPS). Immune-related adverse events (irAEs) were monitored during the study period. Results Cancer patients had a large variation in serum nivolumab concentrations (interquartile range, 12-21 mu g/mL per mg/kg). The serum nivolumab concentration was positively correlated with serum albumin, while negatively associated with serum globulin and immunoglobulin G (IgG). A negative correlation was observed between serum nivolumab and blood lymphocytes. Regarding cachexia progression, the patients with GPS 2 had a higher serum interleukin-6 concentration and a lower serum nivolumab concentration than those with GPS 0 or 1. The GPS, serum IgG, and blood lymphocytes were identified as independent variables for serum nivolumab. The incidence of irAEs was not associated with the nivolumab dose or serum nivolumab. Conclusion Cachexia progression had a negative impact on serum nivolumab in cancer patients. The interindividual variation in serum nivolumab was characterized by cachexia progression in addition to blood components.