CNSC-51. SELINEXOR FOR THE TREATMENT OF GLIOMA: A RETROSPECTIVE CASE SERIES

Abstract BACKGROUND High grade gliomas are aggressive primary brain tumors. Following progression, treatment options are limited and prognosis is poor. The need for novel agents is unmet. Selinexor is an inhibitor of exportin-1 (XPO-1) currently approved for treatment of certain hematologic malignancies. A phase 2 study of single agent selinexor in glioma suggested modest response and variable tolerability. Here, we report our real-world institutional experience with the off-label use of selinexor for glioma. METHODS This is a single-center retrospective case series of patients with glioma treated with oral selinexor from January 1, 2020 to August 1, 2024. RESULTS Twenty-two patients were identified (men=12, women=9). Median age was 55 (range, 33–85), median Karnofsky Performance Status 80 (range, 50–90). Diagnoses included glioblastoma (n=20), H3K27M-altered glioma (n=1), and astrocytoma, IDH-mutated (n=1). Nineteen patients (86%) were treated for relapsed/refractory disease. Three (14%) were treated upfront, prior to progression. Median prior number of therapies was 2 (range, 0 – 5). Median starting dose of Selinexor was 50mg weekly (40 – 80) and median dose at the end of treatment was 70mg weekly (range, 40-80). Six patients (27%) tolerated dose increases and two patients (9%) required dose reductions. Median duration of therapy was 103 days (range, 4 – 636). All patients were given selinexor in combination with other therapy including radiation (n=2), tumor-treating fields (n=1), and medical therapy (n=20). Medical therapies included bevacizumab (n=15), temozolomide (n=10), and other therapies (n=3). Grade 3-4 laboratory toxicities included thrombocytopenia (n=1) and creatinine phosphokinase elevation (n=1). Observed non-laboratory toxicities included nausea (n=5), diarrhea (n=3), fatigue (n=8), gastrointestinal toxicities (n=3), and nephrotoxicity (n=1). CONCLUSION In our single institution experience, selinexor was well tolerated for glioma in conjunction with radiation, bevacizumab, temozolomide, and other medical therapies. No new safety signals were identified. Further research is required to characterize efficacy in patients with glioma.