Cheng Mengfei, Yang Fang, Yang Yanchao, Gao Xinyue, Yu Yang, Wang Nan, Luo Xinyu, Zhang Shuo, Jiang Shuai, Dong Mei
Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Department of Pharmacy, Chongqing University Cancer Hospital, Chongqing, China.
Cancer Chemother Pharmacol. 2024 Jan;93(1):31-39. doi: 10.1007/s00280-023-04590-z. Epub 2023 Sep 23.
Camrelizumab combined with chemotherapy is approved across tumor types. However, only a fraction of patients benefits from immunotherapy, and biomarkers such as the expression of PD-L1, tumor mutational burden, and CXCL11 are expensive and suboptimal specificity for cancer patients. An exposure-response (E-R) relationship has been reported in many immune checkpoint inhibitors (ICIs), and the trough concentrations and other drug exposure metrics are broadly used to guide dosing decisions, assess exposure-outcomes relationships, and ultimately predict outcomes based on those relationships. However, the potential use of trough concentration levels for camrelizumab is still not clear.
Blood samples were obtained at trough levels after doses 3 and 4 from 77 patients with advanced lung cancer who received camrelizumab (200 mg Q3 W) monotherapy or combined with chemotherapy. We optimized a competitive ELISA method to measure the trough concentration.
We found that the trough concentration was steady after 3 dose cycles, and the trough concentration level of camrelizumab was higher in patients who developed immune-related adverse effects (irAEs) than in those who did not (P < 0.05) but was not observed in disease progression and PFS (P > 0.05). Age (< 65 years old), no smoking history, and efficacy evaluation after 4-dose treatment were associated with PFS (P < 0.05), but no significance was observed in other clinical characteristics. Total bilirubin and albumin had an influence on trough concentration, and monocytes and albumin were independent risk factors for PFS (P < 0.05).
Our results suggest that the trough concentration level of camrelizumab might be a risk factor for the occurrence of irAEs in advanced lung cancer, and using the immunotherapy as early as possible may bring better clinical outcomes.
卡瑞利珠单抗联合化疗已获批用于多种肿瘤类型。然而，只有一小部分患者能从免疫治疗中获益，诸如程序性死亡受体配体1（PD-L1）表达、肿瘤突变负荷和CXC趋化因子配体11（CXCL11）等生物标志物对于癌症患者而言成本高昂且特异性欠佳。许多免疫检查点抑制剂（ICI）已报道了暴露-反应（E-R）关系，谷浓度及其他药物暴露指标被广泛用于指导给药决策、评估暴露-结局关系，并最终基于这些关系预测结局。然而，卡瑞利珠单抗谷浓度水平的潜在用途仍不明确。
从77例接受卡瑞利珠单抗（200mg，每3周一次）单药治疗或联合化疗的晚期肺癌患者中，在第3剂和第4剂给药后的谷浓度水平采集血样。我们优化了一种竞争性酶联免疫吸附测定（ELISA）方法来测量谷浓度。
我们发现，3个剂量周期后谷浓度稳定，发生免疫相关不良反应（irAE）的患者中卡瑞利珠单抗的谷浓度水平高于未发生者（P<0.05），但在疾病进展和无进展生存期（PFS）方面未观察到差异（P>0.05）。年龄（<65岁）、无吸烟史以及4剂治疗后的疗效评估与PFS相关（P<0.05），但在其他临床特征方面未观察到显著差异。总胆红素和白蛋白对谷浓度有影响，单核细胞和白蛋白是PFS的独立危险因素（P<0.05）。
我们的结果表明，卡瑞利珠单抗的谷浓度水平可能是晚期肺癌发生irAE的一个危险因素，尽早使用免疫治疗可能带来更好的临床结局。
