Glioblastoma, IDH-wildtype, with a novel MEF2D-NTRK1 gene fusion: a case report

A woman, in her mid-50s, presented with headache, confusion, and unstable gait due to a large right parietal mass subsequently diagnosed histologically as glioblastoma, IDH-wildtype, CNS WHO Grade 4 with an unmethylated MGMT promoter. Next-generation sequencing revealed a rare gene fusion involving myocyte enhancer factor 2D and neurotrophic receptor tyrosine kinase 1 (MEF2D-NTRK1), informing our therapeutic approach. The patient was treated with temozolomide concurrently with radiotherapy, followed by tumor treating fields with adjuvant temozolomide. This report examines the distinctive molecular profile of this patient's glioblastoma, including the remarkable MEF2D-NTRK1 gene fusion, and the treatment options pursued to mitigate disease progression and optimize quality of life. Here, we will discuss the potential for resistance to tyrosine kinase inhibition and the efficacy of first- and second-generation tyrosine kinase inhibitors in relation to this inhibition. Various tyrosine kinase inhibitors, including entrectinib, larotrectinib, repotrectinib, and selitrectinib, along with bevacizumab, were considered to potentially prolong progression-free survival and overall survival and improve quality of life. We expect to highlight the rarity of this case while discussing the effectiveness of second-generation tyrosine kinase inhibitors in high-grade glioblastomas with rare gene fusions. We also hope to identify the appropriate timeline and treatment sequence for post-standard care, given the lack of official guidelines regarding cases this infrequent.