EPCO-02. LONG-TERM DISEASE CONTROL OF LYNCH SYNDROME-ASSOCIATED THALAMIC GLIOBLASTOMA WITH IMMUNOTHERAPY: A CASE STUDY

Abstract Thalamic glioblastoma (GBM) is a highly malignant and rare form of brain cancer, often presenting a poor prognosis due to its deep location near critical neurological structures, limiting gross total resection. Lynch syndrome (LS) is an inherited condition caused by mutations in mismatch repair genes, associated with an increased risk of colorectal and endometrial cancers. 1%-6% of LS cases involve brain tumors, ~56% being GBM. The average survival for LS-associated GBM is 12.1 months (range: 1-41 months), though responders to immunotherapy have shown a median survival of 60 months, compared to 15.5-19 months in non-responders. We discuss the case of a 43-year-old man who presented with right-sided weakness and slurred speech. Brain MRI revealed a growth in the left thalamus, confirmed as GBM via biopsy. He began six weeks of concurrent chemoradiation with temozolomide (TMZ), followed by adjuvant TMZ. Germline genetic testing revealed LS with an MSH6 c.1754T>C (p.Leu585Pro) mutation; next-generation sequencing (NGS) confirmed high microsatellite instability (MSI-high), and tumor mutational burden (TMB) >150. He also had 2 ATRX alterations (exon 28/p.W2098* and exon 15/p.E1513*). TMZ was discontinued, and he began treatment with bevacizumab and pembrolizumab every three weeks for 1.5 years. MRI revealed nonspecific enhancement in the bilateral cerebellum, suggesting autoimmune cerebellitis, prompting discontinuation of pembrolizumab. Four months later, he began lomustine and bevacizumab for six cycles (nine months). Brain MRI demonstrated a significant reduction in cerebellar enhancement and stable post-treatment changes in the left thalamus. He has been off treatment and on active surveillance with brain MRI every three months for the past 1.5 years and is now 4.5 years post-diagnosis. He continues to work full-time as a software engineer and is doing well. This case highlights the potential efficacy of immunotherapy and TMZ avoidance, which could reduce hypermutation and support long-term disease control of LS-associated thalamic GBM.