James Yu, Robin Park, Ruoyu Miao, Iman Imanirad, Moazzam Shahzad, Jose M Laborde, Todd C Knepper, Christine M Walko, Richard Kim
{"title":"仅凭血液肿瘤突变负荷不能很好地预测胃肠道肿瘤患者对免疫检查点抑制剂反应的生物标志物","authors":"James Yu, Robin Park, Ruoyu Miao, Iman Imanirad, Moazzam Shahzad, Jose M Laborde, Todd C Knepper, Christine M Walko, Richard Kim","doi":"10.1097/CJI.0000000000000532","DOIUrl":null,"url":null,"abstract":"<p><p>There has been a controversy about the predictive value of tissue-TMB-H for immune checkpoint inhibitors (ICIs) with limited data regarding blood-TMB (bTMB) in GI tumors. We aim to evaluate the predictive value of bTMB compared with MSI-H in GI tumors. Patients with unresectable/metastatic GI cancer, harboring either MSS with bTMB-H (≥10 mut/Mb) or dMMR/MSI-H who received ICI were included. We compared ICIs' efficacy between MSS-bTMB-H (N=45) versus MSI-H (N=50) in GI tumors. Ninety-five patients were identified with the majority having colorectal (49.5%) or esophagogastric (34.7%) cancers. MSS-bTMB-H group had more esophagogastric cancer and later-line ICI recipients, with no significant differences in other known prognostic variables. At a median follow-up of 9.4 months, MSI-H group showed superior ORR (58.0% vs. 26.7%), DCR (84.0% vs. 42.2%), DoR (not-reached vs. 7.6 mo), PFS (22.5 vs. 3.8 mo), and OS (Not-reached vs. 10.1 mo) compared with MSS-bTMB-H. Multivariable analysis showed that MSI-H was an independent favorable factor over MSS-bTMB-H for PFS (HR=0.31, CI 0.15-0.63, P =0.001) and OS (HR=0.33, CI 0.14-0.80, P =0.014). MSI-H group showed favorable outcomes compared with MSS-bTMB-16+ (ORR: 58.0% vs. 26.9%; DCR: 84.0% vs. 42.3%; PFS:22.5 vs. 4.0 mo) and MSS-bTMB-20+ (ORR: 58.0% vs. 31.6%; DCR: 84.0% vs. 42.1%; PFS:22.5 vs. 3.2 mo). There was no difference between MSS-bTMB10-15 compared with MSS-bTMB-16+ in ORR, DCR, and PFS, or between MSS-bTMB10-19 compared with MSS-bTMB20+. Regardless of bTMB cutoff at 10, 16, or 20, bTMB-H did not appear to be a predictive biomarker in MSS GI tumors in this retrospective analysis.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"378-383"},"PeriodicalIF":3.2000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Blood Tumor Mutational Burden Alone Is Not a Good Predictive Biomarker for Response to Immune Checkpoint Inhibitors in Patients With Gastrointestinal Tumors.\",\"authors\":\"James Yu, Robin Park, Ruoyu Miao, Iman Imanirad, Moazzam Shahzad, Jose M Laborde, Todd C Knepper, Christine M Walko, Richard Kim\",\"doi\":\"10.1097/CJI.0000000000000532\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>There has been a controversy about the predictive value of tissue-TMB-H for immune checkpoint inhibitors (ICIs) with limited data regarding blood-TMB (bTMB) in GI tumors. We aim to evaluate the predictive value of bTMB compared with MSI-H in GI tumors. Patients with unresectable/metastatic GI cancer, harboring either MSS with bTMB-H (≥10 mut/Mb) or dMMR/MSI-H who received ICI were included. We compared ICIs' efficacy between MSS-bTMB-H (N=45) versus MSI-H (N=50) in GI tumors. Ninety-five patients were identified with the majority having colorectal (49.5%) or esophagogastric (34.7%) cancers. MSS-bTMB-H group had more esophagogastric cancer and later-line ICI recipients, with no significant differences in other known prognostic variables. At a median follow-up of 9.4 months, MSI-H group showed superior ORR (58.0% vs. 26.7%), DCR (84.0% vs. 42.2%), DoR (not-reached vs. 7.6 mo), PFS (22.5 vs. 3.8 mo), and OS (Not-reached vs. 10.1 mo) compared with MSS-bTMB-H. Multivariable analysis showed that MSI-H was an independent favorable factor over MSS-bTMB-H for PFS (HR=0.31, CI 0.15-0.63, P =0.001) and OS (HR=0.33, CI 0.14-0.80, P =0.014). MSI-H group showed favorable outcomes compared with MSS-bTMB-16+ (ORR: 58.0% vs. 26.9%; DCR: 84.0% vs. 42.3%; PFS:22.5 vs. 4.0 mo) and MSS-bTMB-20+ (ORR: 58.0% vs. 31.6%; DCR: 84.0% vs. 42.1%; PFS:22.5 vs. 3.2 mo). There was no difference between MSS-bTMB10-15 compared with MSS-bTMB-16+ in ORR, DCR, and PFS, or between MSS-bTMB10-19 compared with MSS-bTMB20+. Regardless of bTMB cutoff at 10, 16, or 20, bTMB-H did not appear to be a predictive biomarker in MSS GI tumors in this retrospective analysis.</p>\",\"PeriodicalId\":15996,\"journal\":{\"name\":\"Journal of Immunotherapy\",\"volume\":\" \",\"pages\":\"378-383\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Immunotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/CJI.0000000000000532\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CJI.0000000000000532","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
组织TMB-H对免疫检查点抑制剂(ICIs)的预测价值一直存在争议,而有关消化道肿瘤血液TMB(bTMB)的数据却很有限。我们旨在评估 bTMB 与 MSI-H 相比在消化道肿瘤中的预测价值。我们纳入了接受 ICI 的不可切除/转移性消化道癌症患者,这些患者携带有 bTMB-H(≥10 突变/Mb)的 MSS 或 dMMR/MSI-H。我们比较了消化道肿瘤中MSS-bTMB-H(45例)与MSI-H(50例)的ICI疗效。结果发现,95 名患者大部分患有结直肠癌(49.5%)或食管胃癌(34.7%)。MSS-bTMB-H组食管胃癌患者较多,接受 ICI 治疗的时间也较晚,其他已知预后变量无明显差异。在中位随访9.4个月时,MSI-H组的ORR(58.0% vs. 26.7%)、DCR(84.0% vs. 42.2%)、DoR(未达到 vs. 7.6个月)、PFS(22.5 vs. 3.8个月)和OS(未达到 vs. 10.1个月)均优于MSS-bTMB-H组。多变量分析显示,与MSS-bTMB-H相比,MSI-H是PFS(HR=0.31,CI 0.15-0.63,P=0.001)和OS(HR=0.33,CI 0.14-0.80,P=0.014)的独立有利因素。与MSS-bTMB-16+(ORR:58.0% vs. 26.9%;DCR:84.0% vs. 42.3%;PFS:22.5月 vs. 4.0月)和MSS-bTMB-20+(ORR:58.0% vs. 31.6%;DCR:84.0% vs. 42.1%;PFS:22.5月 vs. 3.2月)相比,MSI-H组显示出良好的结果。在ORR、DCR和PFS方面,MSS-bTMB10-15与MSS-bTMB-16+相比没有差异,MSS-bTMB10-19与MSS-bTMB20+相比也没有差异。在这项回顾性分析中,无论 bTMB 临界值是 10、16 还是 20,bTMB-H 似乎都不是 MSS 消化道肿瘤的预测性生物标志物。
Blood Tumor Mutational Burden Alone Is Not a Good Predictive Biomarker for Response to Immune Checkpoint Inhibitors in Patients With Gastrointestinal Tumors.
There has been a controversy about the predictive value of tissue-TMB-H for immune checkpoint inhibitors (ICIs) with limited data regarding blood-TMB (bTMB) in GI tumors. We aim to evaluate the predictive value of bTMB compared with MSI-H in GI tumors. Patients with unresectable/metastatic GI cancer, harboring either MSS with bTMB-H (≥10 mut/Mb) or dMMR/MSI-H who received ICI were included. We compared ICIs' efficacy between MSS-bTMB-H (N=45) versus MSI-H (N=50) in GI tumors. Ninety-five patients were identified with the majority having colorectal (49.5%) or esophagogastric (34.7%) cancers. MSS-bTMB-H group had more esophagogastric cancer and later-line ICI recipients, with no significant differences in other known prognostic variables. At a median follow-up of 9.4 months, MSI-H group showed superior ORR (58.0% vs. 26.7%), DCR (84.0% vs. 42.2%), DoR (not-reached vs. 7.6 mo), PFS (22.5 vs. 3.8 mo), and OS (Not-reached vs. 10.1 mo) compared with MSS-bTMB-H. Multivariable analysis showed that MSI-H was an independent favorable factor over MSS-bTMB-H for PFS (HR=0.31, CI 0.15-0.63, P =0.001) and OS (HR=0.33, CI 0.14-0.80, P =0.014). MSI-H group showed favorable outcomes compared with MSS-bTMB-16+ (ORR: 58.0% vs. 26.9%; DCR: 84.0% vs. 42.3%; PFS:22.5 vs. 4.0 mo) and MSS-bTMB-20+ (ORR: 58.0% vs. 31.6%; DCR: 84.0% vs. 42.1%; PFS:22.5 vs. 3.2 mo). There was no difference between MSS-bTMB10-15 compared with MSS-bTMB-16+ in ORR, DCR, and PFS, or between MSS-bTMB10-19 compared with MSS-bTMB20+. Regardless of bTMB cutoff at 10, 16, or 20, bTMB-H did not appear to be a predictive biomarker in MSS GI tumors in this retrospective analysis.
期刊介绍:
Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.