Pembrolizumab efficacy in a tumor mutation burden-high glioblastoma patient: A case study and implications for precision oncology.

in Cancer science by Akihiro Nishiyama, Shigeki Sato, Hiroyuki Sakaguchi, Hiroshi Kotani, Kaname Yamashita, Koushiro Ohtsubo, Tomoko Sekiya, Atsushi Watanabe, Atsushi Tajima, Chie Shimaguchi, Keishi Mizuguchi, Hiroko Ikeda, Masashi Kinoshita, Mitsutoshi Nakada, Shinji Takeuchi

TLDR

  • This study is about a person with a type of brain tumor called glioblastoma. They had a lot of mutations in their DNA, which made them more likely to respond to a medicine called pembrolizumab. Even though they had already taken another medicine called temozolomide, which can sometimes make tumors resistant to pembrolizumab, they still responded well to it. This study shows that sometimes, it's better to use a different medicine based on a person's specific genetic makeup, rather than following a one-size-fits-all approach.

Abstract

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.

Overview

  • The study focuses on a GBM patient with high TMB and dMMR who exhibited a significant response to pembrolizumab despite prior TMZ treatment. The methodology involves a case study of a single patient with genomic profiling and clinical evaluation. The primary objective is to assess the efficacy of pembrolizumab in this patient and its potential implications for GBM treatment paradigms.

Comparative Analysis & Findings

  • The patient's response to pembrolizumab was compared to the prior TMZ treatment, and the results showed a significant improvement in disease progression. The rapid Ki67 positivity was markedly countered by the positive outcome of pembrolizumab treatment.

Implications and Future Directions

  • The study highlights the potential of precision oncology in GBM patients with high TMB and dMMR, and underscores the importance of comprehensive genomic profiling in guiding clinical decisions. Future research should focus on expanding the understanding of the mechanisms underlying the response to ICIs in GBM and identifying additional biomarkers for personalized treatment.
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