Blood tumor mutation burden can predict the clinical response to immune checkpoint inhibitors in advanced non-small cell lung cancer patients
Blood tumor mutation burden can predict the clinical response to immune checkpoint inhibitors in advanced non-small cell lung cancer patients
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DOI：
10.1007/s00262-021-02943-2
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发表时间：
2021-04-25
影响因子：
5.8
通讯作者：
Zhou, Jianying
中科院分区：
文献类型：
--
作者：
Chen, Xi;Fang, Liangjie;Zhou, Jianying
全外显子组测序（WES）评估组织肿瘤突变负荷（tTMB）被认为是tTMB测量的金标准方法，可以预测免疫检查点抑制剂（ICIs）的临床疗效。许多研究已经调查了利用大型面板评估TMB的可行性，但得到了相互矛盾的结果。此外，血液TMB （bTMB）是否也可以作为非小细胞肺癌的预测性生物标志物尚未确定。方法纳入56例接受ICIs治疗的晚期NSCLC患者，包括一个探索性队列（n = 42）和一个小型独立验证队列（n = 14）。使用由520个癌症相关基因组成的小组（OncoScreen）对ICI治疗前收集的肿瘤和血浆样本进行下一代测序，以评估tTMB/bTMB。同时对肿瘤样本进行WES检测作为参考。结果WES与OncoScreen的tTMB呈正相关。oncoscreen衍生的tTMB与oncoscreen衍生的bTMB呈正相关。oncoscreen衍生的tTMB >= 7个突变/Mb （p = 0.003）或bTMB >= 11个突变/Mb （p = 0.0029）的患者具有优越的无进展生存期（PFS）。在小型验证队列中，oncoscreen衍生的bTMB患者>= 11个突变/Mb表现出更长的PFS (p = 0.192)，差异不显著。在所有42例可获得bTMB和PFS的患者中，bTMB >= 11个突变/Mb的患者的PFS明显长于bTMB < 11个突变/Mb的患者（p = 0.011）。结论本研究证实了采用大面板估算TMB的可行性。我们还证明了bTMB可以作为预测非小细胞肺癌中ICIs疗效的潜在生物标志物。
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 >= 7 mutations/Mb (p = 0.003) or bTMB >= 11 mutations/Mb (p = 0.0029) had superior progression-free survival (PFS). In the small validation cohort, patients with OncoScreen-derived bTMB >= 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 >= 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.