Cao Jinlong, Yang Xin, Chen Siyu, Wang Jirong, Fan Xinpeng, Fu Shengjun, Yang Li
Department of Urology, The Second Hospital of Lanzhou University, No.82 Cuiyingmen, Lanzhou, Gansu 730000, China; Key Laboratory of Urological Diseases of Gansu Provincial, Lanzhou 730000, China.
Reproductive Medicine Center, The Second Hospital of Lanzhou University, Lanzhou 730000, China.
Transl Oncol. 2022 Jun;20:101375. doi: 10.1016/j.tranon.2022.101375. Epub 2022 Mar 23.
To explore the predictive efficacy of tumor mutation burden (TMB) as a potential biomarker for cancer patients treated with Immune checkpoint inhibitors (ICIs).
We systematically searched PubMed, Cochrane Library, Embase and Web of Science for clinical studies (published between Jan 1, 2014 and Aug 30, 2021) comparing immunotherapy patients with high TMB to patients with low TMB. Our main endpoints were objective response rate (ORR), durable clinical benefit (DCB), overall survival (OS) and progress-free Survival (PFS). Moreover, we downloaded simple nucleotide variation (SNV) data of 33 major cancer types from the TCGA database as non-ICIs group, and compared the high TMB patients' OS between the non-ICIs group and meta-analysis results.
Of 10,450 identified studies, 41 were eligible and were included in our analysis (7713 participants). Compared with low TMB patients receiving ICIs, high TMB yielded a better ORR (RR = 2.73; 95% CI: 2.31-3.22; P = 0.043) and DCB (RR = 1.93; 95% CI: 1.64-2.28; P = 0.356), and a significantly increased OS (HR =0.24; 95% CI: 0.21-0.28; P < 0.001) and PFS (HR = 0.38; 95% CI: 0.34-0.42; P < 0.001). Furthermore, compared with non-ICIs group from the TCGA database, immunotherapy can improve OS in some cancer types with high TMB and better prognosis, including colorectal cancer, gastric cancer, lung cancer, melanoma and pan-cancer.
TMB is a promising therapeutic and prognostic biomarker for immunotherapy, which indicates a better ORR, DCB, OS and PFS. If there is a standard for TMB assessment and cut-off, it could improve the management of different cancers.
探讨肿瘤突变负荷（TMB）作为免疫检查点抑制剂（ICI）治疗癌症患者潜在生物标志物的预测效能。
我们系统检索了PubMed、Cochrane图书馆、Embase和Web of Science数据库，查找2014年1月1日至2021年8月30日期间发表的比较高TMB免疫治疗患者与低TMB患者的临床研究。我们的主要终点是客观缓解率（ORR）、持久临床获益（DCB）、总生存期（OS）和无进展生存期（PFS）。此外，我们从TCGA数据库下载了33种主要癌症类型的单核苷酸变异（SNV）数据作为非ICI组，并比较了非ICI组与荟萃分析结果中高TMB患者的OS。
在10450项已确定的研究中，41项符合条件并纳入我们的分析（7713名参与者）。与接受ICI的低TMB患者相比，高TMB患者的ORR更好（RR = 2.73；95%CI：2.31 - 3.22；P = 0.043），DCB更好（RR = 1.93；95%CI：1.64 - 2.28；P = 0.356），OS显著延长（HR = 0.24；95%CI：0.21 - 0.28；P < 0.001），PFS也显著延长（HR = 0.38；95%CI：0.34 - 0.42；P < 0.001）。此外，与TCGA数据库中的非ICI组相比，免疫治疗可改善某些高TMB且预后较好的癌症类型的OS，包括结直肠癌、胃癌、肺癌、黑色素瘤和泛癌。
TMB是免疫治疗中一个有前景的治疗和预后生物标志物，预示着更好的ORR、DCB、OS和PFS。如果有TMB评估和临界值的标准，可能会改善不同癌症的治疗管理。
