Nishiyama Akihiro, Sato Shigeki, Sakaguchi Hiroyuki, Kotani Hiroshi, Yamashita Kaname, Ohtsubo Koushiro, Sekiya Tomoko, Watanabe Atsushi, Tajima Atsushi, Shimaguchi Chie, Mizuguchi Keishi, Ikeda Hiroko, Kinoshita Masashi, Nakada Mitsutoshi, Takeuchi Shinji
Department of Medical Oncology, Kanazawa University Hospital, Kanazawa, Japan.
Division of Clinical Genetics, Kanazawa University Hospital, Kanazawa, Japan.
Cancer Sci. 2025 Jan;116(1):271-276. doi: 10.1111/cas.16370. Epub 2024 Oct 25.
A glioblastoma (GBM) patient with a high tumor mutation burden (TMB-high) and mismatch repair deficiency (dMMR) exhibited a significant response to pembrolizumab, an immune checkpoint inhibitor (ICI), despite prior treatment with temozolomide (TMZ), known to induce hypermutation and potential resistance to ICIs. The rapid disease progression, indicated by 80% Ki67 positivity, was markedly countered by the positive outcome of pembrolizumab treatment. This case challenges traditional GBM treatment paradigms, demonstrating the potential of precision oncology in patients with significant TMB and dMMR, and underscores the importance of comprehensive genomic profiling in guiding clinical decisions in GBM management.
一名具有高肿瘤突变负荷（TMB高）和错配修复缺陷（dMMR）的胶质母细胞瘤（GBM）患者，尽管之前接受过已知会诱导高突变并可能导致对免疫检查点抑制剂（ICI）产生耐药性的替莫唑胺（TMZ）治疗，但对帕博利珠单抗（一种ICI）仍表现出显著反应。由80% Ki67阳性所表明的快速疾病进展，被帕博利珠单抗治疗的阳性结果显著对抗。该病例挑战了传统的GBM治疗模式，证明了精准肿瘤学在具有显著TMB和dMMR患者中的潜力，并强调了全面基因组分析在指导GBM管理临床决策中的重要性。
