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Investigation on potential biomarkers of hyperprogressive disease (HPD) triggered by immune checkpoint inhibitors (ICIs)

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Abstract

Purpose

This project aimed to survey the clinical characteristics and survivals of hyperprogressive disease (HPD) mediated by immune checkpoint inhibitors (ICIs) in an attempt to explore the potential predictors.

Methods

After searching PubMed, MEDLINE, Google Scholar and Cochrane Library databases, 12 studies incorporating 1766 individuals were enrolled. The data were analyzed with Review manager 5.3 software.

Results

The results revealed HPD correlated with previous metastatic sites > 2 (OR = 1.86, 95% CI 1.33–2.59, P = 0.0003), liver metastasis (OR = 3.35, 95% CI 2.09–5.35, P < 0.00001), Royal Marsden Hospital (RMH) score ≥ 2 (OR = 2.80, 95% CI 1.85–4.23, P < 0.00001), higher ECOG PS (OR = 1.60, 95% CI 1.13–2.27, P = 0.008) and LDH > upper limits of normal (ULN) (OR = 2.32, 95% CI 1.51–3.58, P = 0.0001). Instead, HPD was unrelated to gender, age, smoking status, PD-L1 expression, therapy, neutrophil-to-lymphocyte ratio, the histology, the status of EGFR, ALK and KRAS in non-small cell lung cancer and HER-2 expression in advanced gastric cancer. Moreover, HPD was evidently correlated with a shorter OS (HR = 2.92, 95% CI 1.79–4.76, P < 0.0001) and PFS (HR = 3.62, 95% CI 2.79–4.68, P < 0.00001). The same phenomena existed in stratified studies based on study regions and tumor types.

Conclusions

This study demonstrated that HPD was related to the number of prior metastatic sites > 2, liver metastasis, RMH score ≥ 2, higher ECOG PS score and LDH > ULN. Moreover, HPD was correlated with a poor OS and PFS in patients following ICI therapy.

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Authors and Affiliations

  1. Department of Oncology, Molecular Oncology Research Institute, the First Affiliated Hospital, Fujian Medical University, Chazhong Road No 20, Fuzhou 350005, Fujian, China

    J. Liu, Q. Wu, S. Wu & X. Xie

  2. Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Chazhong Road No 20, Fuzhou 350005, Fujian, China

    X. Xie

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  1. J. Liu
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  2. Q. Wu
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  3. S. Wu
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  4. X. Xie
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Contributions

XX contributed to the study conception and design. Material preparation, data collection and analysis were performed by JL, QW, SW and XX. The first draft of the manuscript was written by JL and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to X. Xie.

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Liu, J., Wu, Q., Wu, S. et al. Investigation on potential biomarkers of hyperprogressive disease (HPD) triggered by immune checkpoint inhibitors (ICIs). Clin Transl Oncol 23, 1782–1793 (2021). https://doi.org/10.1007/s12094-021-02579-9

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  • DOI: https://doi.org/10.1007/s12094-021-02579-9

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