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Correlation analysis between camrelizumab trough concentration levels and efficacy or safety in East Asian patients with advanced lung cancer

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by the Project of Beijing Medical Award Foundation (YXJL-2022-0187-0013), Beijing Hongdingxiang Public Welfare Development Center (BJ-HDX-20220437) and The General Program of Harbin Medical University Cancer Hospital Haiyan Fund (JJMS2022-19). The authors are grateful to the patients and their families for their participation in this study. The study was approved by the Ethics Committee of Harbin Medical University Cancer Hospital (KY2022-48).

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Author notes

  1. Mengfei Cheng, Fang Yang, and Yanchao Yang have contributed equally.

Authors and Affiliations

  1. Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China

    Mengfei Cheng, Yanchao Yang, Xinyue Gao, Yang Yu, Nan Wang, Xinyu Luo, Shuo Zhang, Shuai Jiang & Mei Dong

  2. Department of Pharmacy, Chongqing University Cancer Hospital, Chongqing, China

    Mengfei Cheng

  3. The First Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China

    Fang Yang

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  1. Mengfei Cheng
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Contributions

MD and SJ: designed the study and wrote the article. MC, FY and YY: performed the experiment. Blood samples and patient information were collected by XG, YY, NW and XL, data summary and statistical analysis were completed by MC and SZ. All authors read and approved the article and agreed to be accountable for all aspects of the research in ensuring that the accuracy or integrity of any part of the work was appropriately investigated and resolved.

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Correspondence to Shuai Jiang or Mei Dong.

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Cheng, M., Yang, F., Yang, Y. et al. Correlation analysis between camrelizumab trough concentration levels and efficacy or safety in East Asian patients with advanced lung cancer. Cancer Chemother Pharmacol 93, 31–39 (2024). https://doi.org/10.1007/s00280-023-04590-z

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  • DOI: https://doi.org/10.1007/s00280-023-04590-z

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