高突变和错配修复突变的复发性高级别胶质瘤中检查点抑制剂治疗失败
Checkpoint inhibitor failure in hypermutated and mismatch repair-mutated recurrent high-grade gliomas.
作者信息
Ahmad Haroon, Fadul Camilo E, Schiff David, Purow Benjamin
机构信息
University of Virginia School of Medicine, Division of Neuro-Oncology, Department of Neurology, University of Virginia, Charlottesville.
出版信息
Neurooncol Pract. 2019 Dec;6(6):424-427. doi: 10.1093/nop/npz016. Epub 2019 Apr 7.
BACKGROUND
Recurrent high-grade gliomas in adults remain a deadly cancer with median survival of less than 1 year. In the absence of effective agents, immunotherapy with checkpoint inhibitors has been adopted as a potentially beneficial next step for recurrences with hypermutated or mismatch repair-mutated phenotypes. The rationale for their use, however, is based on case reports and studies with other types of cancer.
METHODS
We reviewed 4 cases of hypermutated or mismatch repair-mutated recurrent high-grade gliomas treated with checkpoint inhibitors.
RESULTS
All cases had recurrent high-grade glioma that harbored either a hypermutated phenotype and/or a mismatch repair mutation. Treatment with checkpoint inhibitor therapy resulted in no significant response.
CONCLUSIONS
In our experience, hypermutated or mismatch repair-mutated high-grade gliomas in adults do not respond to checkpoint inhibitors alone. This lack of efficacy is in agreement with underwhelming results of clinical trials examining checkpoint inhibitors in high-grade gliomas. The case reports of responders have been in pediatric patients with glioma and are likely a different subtype altogether.
背景
成人复发性高级别胶质瘤仍然是一种致命的癌症，中位生存期不到1年。在缺乏有效药物的情况下，对于具有高突变或错配修复突变表型的复发患者，采用检查点抑制剂免疫疗法作为潜在的有益下一步治疗方案。然而，其使用的理论依据基于病例报告以及对其他类型癌症的研究。
方法
我们回顾了4例接受检查点抑制剂治疗的高突变或错配修复突变的复发性高级别胶质瘤病例。
结果
所有病例均为复发性高级别胶质瘤，具有高突变表型和/或错配修复突变。检查点抑制剂治疗未产生显著反应。
结论
根据我们的经验，成人高突变或错配修复突变的高级别胶质瘤对单独的检查点抑制剂无反应。这种疗效不佳与在高级别胶质瘤中检查点抑制剂的临床试验结果不尽人意相符。有反应的病例报告均为儿童胶质瘤患者，可能完全是不同的亚型。
Zotero 插件