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25.04.2021 | Original Article

Blood tumor mutation burden can predict the clinical response to immune checkpoint inhibitors in advanced non-small cell lung cancer patients

verfasst von: Xi Chen, Liangjie Fang, Yanping Zhu, Zhang Bao, Qing Wang, Rong Liu, Wenjia Sun, Haiwei Du, Jing Lin, Bing Yu, Songan Chen, Jianya Zhou, Jianying Zhou

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 12/2021

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Abstract

Background

Tissue tumor mutation burden (tTMB) assessed by whole-exome sequencing (WES), which has been regarded as the gold standard method of tTMB measurement, can predict the clinical benefits of immune checkpoint inhibitors (ICIs). Multiple studies have investigated the feasibility of utilizing large panels to evaluate TMB but have obtained conflicting results. Furthermore, whether blood TMB (bTMB) can also be a predictive biomarker in NSCLC has not been determined.

Methods

Fifty-six advanced NSCLC patients treated with ICIs were enrolled, including an exploratory cohort (n = 42) and a small independent validation cohort (n = 14). Next-generation sequencing was performed on tumor and plasma samples collected prior to ICI treatment using a panel consisting of 520 cancer-related genes (OncoScreen) to evaluate tTMB/bTMB. WES was also performed on tumor samples to serve as references.

Results

A positive correlation between tTMB derived from WES and OncoScreen was observed. OncoScreen-derived tTMB showed a positive correlation with OncoScreen-derived bTMB. Patients with OncoScreen-derived tTMB \(\ge\) 7 mutations/Mb (p = 0.003) or bTMB \(\ge\) 11 mutations/Mb (p = 0.0029) had superior progression-free survival (PFS). In the small validation cohort, patients with OncoScreen-derived bTMB \(\ge\) 11 mutations/Mb exhibited longer PFS (p = 0.192) with a nonsignificant difference. In all 42 patients who had available bTMB and PFS, patients with bTMB \(\ge\) 11 mutations/Mb had significantly longer PFS (p = 0.011) than those with bTMB \(<\) 11 mutations/Mb.

Conclusion

Our study confirmed the feasibility of using large panels to estimate TMB. We also demonstrated that bTMB can serve as a potential biomarker for predicting the efficacy of ICIs in NSCLC.

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Titel: Blood tumor mutation burden can predict the clinical response to immune checkpoint inhibitors in advanced non-small cell lung cancer patients
verfasst von: Xi Chen
Liangjie Fang
Yanping Zhu
Zhang Bao
Qing Wang
Rong Liu
Wenjia Sun
Haiwei Du
Jing Lin
Bing Yu
Songan Chen
Jianya Zhou
Jianying Zhou
Publikationsdatum: 25.04.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 12/2021
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-02943-2

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Blood tumor mutation burden can predict the clinical response to immune checkpoint inhibitors in advanced non-small cell lung cancer patients