Kim Jong Yeob, Kronbichler Andreas, Eisenhut Michael, Hong Sung Hwi, van der Vliet Hans J, Kang Jeonghyun, Shin Jae Il, Gamerith Gabriele
Yonsei University College of Medicine, Seoul 03722, Korea.
Department of Internal Medicine IV, Medical University Innsbruck, 6020 Innsbruck, Austria.
Cancers (Basel). 2019 Nov 15;11(11):1798. doi: 10.3390/cancers11111798.
Tumor mutational burden (TMB) is a genomic biomarker that predicts favorable responses to immune checkpoint inhibitors (ICIs). Here, we set out to assess the predictive value of TMB on long-term survival outcomes in patients undergoing ICIs. We systematically searched PubMed, Embase, CENTRAL and clinicaltrials.gov from inception to 6 August 2019. We included retrospective studies or clinical trials of ICIs that reported hazard ratios (HRs) for overall survival (OS) and/or progression-free survival (PFS) according to TMB. Data on 5712 patients from 26 studies were included. Among patients who received ICIs, high TMB groups showed better OS (HR 0.53, 95% CI 0.42 to 0.67) and PFS (HR 0.52, 95% CI 0.40 to 0.67) compared to low TMB groups. In patients with high TMB, those who received ICIs had a better OS (HR 0.69, 95% CI 0.50 to 0.95) and PFS (HR = 0.66, 95% CI = 0.47 to 0.92) compared to those who received chemotherapy alone, while in patients with low TMB, such ICI benefits of OS or PFS were not statistically significant. In conclusion, TMB may be an effective biomarker to predict survival in patients undergoing ICI treatment. The role of TMB in identifying patient groups who may benefit from ICIs should be determined in future randomized controlled trials.
肿瘤突变负荷（TMB）是一种基因组生物标志物，可预测对免疫检查点抑制剂（ICI）的良好反应。在此，我们着手评估TMB对接受ICI治疗患者长期生存结局的预测价值。我们系统检索了从创刊至2019年8月6日的PubMed、Embase、CENTRAL和ClinicalTrials.gov。我们纳入了报告了根据TMB得出的总生存期（OS）和/或无进展生存期（PFS）风险比（HR）的ICI回顾性研究或临床试验。纳入了来自26项研究的5712例患者的数据。在接受ICI治疗的患者中，与低TMB组相比，高TMB组显示出更好的OS（HR 0.53，95%CI 0.42至0.67）和PFS（HR 0.52，95%CI 0.40至0.67）。在高TMB患者中，与单纯接受化疗的患者相比，接受ICI治疗的患者具有更好的OS（HR 0.69，95%CI 0.50至0.95）和PFS（HR = 0.66，95%CI = 0.47至0.92），而在低TMB患者中，ICI在OS或PFS方面的益处无统计学意义。总之，TMB可能是预测接受ICI治疗患者生存的有效生物标志物。TMB在识别可能从ICI中获益的患者群体中的作用应在未来的随机对照试验中确定。
