Immunotherapy induces durable responses in a subset of patients with cancer. High tumor mutational burden (TMB) may be a response biomarker for PD-1/PD-L1 blockade in tumors such as melanoma and non–small cell lung cancer (NSCLC). Our aim was to examine the relationship between TMB and outcome in diverse cancers treated with various immunotherapies. We reviewed data on 1,638 patients who had undergone comprehensive genomic profiling and had TMB assessment. Immunotherapy-treated patients ( N = 151) were analyzed for response rate (RR), progression-free survival (PFS), and overall survival (OS). Higher TMB was independently associated with better outcome parameters (multivariable analysis). The RR for patients with high (≥20 mutations/mb) versus low to intermediate TMB was 22/38 (58%) versus 23/113 (20%; P = 0.0001); median PFS, 12.8 months vs. 3.3 months ( P ≤ 0.0001); median OS, not reached versus 16.3 months ( P = 0.0036). Results were similar when anti-PD-1/PD-L1 monotherapy was analyzed ( N = 102 patients), with a linear correlation between higher TMB and favorable outcome parameters; the median TMB for responders versus nonresponders treated with anti-PD-1/PD-L1 monotherapy was 18.0 versus 5.0 mutations/mb ( P < 0.0001). Interestingly, anti-CTLA4/anti-PD-1/PD-L1 combinations versus anti-PD-1/PD-L1 monotherapy was selected as a factor independent of TMB for predicting better RR (77% vs. 21%; P = 0.004) and PFS ( P = 0.024). Higher TMB predicts favorable outcome to PD-1/PD-L1 blockade across diverse tumors. Benefit from dual checkpoint blockade did not show a similarly strong dependence on TMB. Mol Cancer Ther; 16(11); 2598–608. ©2017 AACR . This article is featured in Highlights of This Issue, [p. 2327][1] [1]: /lookup/volpage/16/2327?iss=11

中文翻译：

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肿瘤突变负担是多种癌症对免疫治疗反应的独立预测因子。

免疫疗法在一部分癌症患者中引起持久的反应。高肿瘤突变负担（TMB）可能是黑色素瘤和非小细胞肺癌（NSCLC）等肿瘤中PD-1 / PD-L1阻断的反应生物标志物。我们的目的是检查在用各种免疫疗法治疗的各种癌症中，TMB与预后之间的关系。我们回顾了有关1638例患者的数据，这些患者均接受了全面的基因组分析并进行了TMB评估。分析了接受免疫疗法治疗的患者（N = 151）的缓解率（RR），无进展生存期（PFS）和总生存期（OS）。较高的TMB与较好的结局参数独立相关（多变量分析）。高（≥20个突变/ mb）与低至中级TMB的患者的RR为22/38（58％）对23/113（20％； P = 0.0001）；PFS中位数，为12.8个月，而前值为3。3个月（P≤0.0001）; 中位OS，未达到与16.3个月相比（P = 0.0036）。分析抗PD-1 / PD-L1单一疗法的结果相似（N = 102例患者），较高的TMB与良好的预后参数之间存在线性相关性。用抗PD-1 / PD-L1单药治疗的应答​​者和非应答者的TMB中位数分别为18.0对5.0突变/ mb（P <0.0001）。有趣的是，选择抗CTLA4 /抗PD-1 / PD-L1组合与抗PD-1 / PD-L1单一疗法作为独立于TMB的因素来预测更好的RR（77％比21％； P = 0.004 ）和PFS（P = 0.024）。较高的TMB预测跨多种肿瘤的PD-1 / PD-L1阻断疗效良好。双重检查站封锁带来的好处并未显示出对TMB的强烈依赖。分子癌疗法；16（11）; 2598–608。©2017 AACR。本文在本期要点[p。2327] [1] [1]：/ lookup / volpage / 16/2327？iss = 11