Objectives/Goals: To assess the safety, tolerability, and adverse effects of adding acetazolamide to temozolomide in newly diagnosed MGMT-methylated malignant glioma, and to explore efficacy, survival outcomes, and Bcl-3 as a potential predictive biomarker. Methods/Study Population: Adults (>18 y) with newly diagnosed, MGMT-methylated, IDH-wildtype glioblastoma, and Karnofsky performance status > 60 receiving standard temozolomide (TMZ) + radiation (RT) were enrolled. Sixty patients (24 initial, 36 subsequent) received acetazolamide (ACZ) twice daily starting on the day of adjuvant TMZ initiation. ACZ began at 250 mg BID for 1 week, then escalated to 500 mg BID, given on days 1–21 of each 28-day cycle (TMZ days 1–5), for up to 6 cycles if not limited by tumor progression/toxicity. Clinical and MRI follow-up occurred every 2 months. Results/Anticipated Results: Preliminary data (initial 24 patients) have shown that no patient had a dose-limiting toxicity. Adverse events were consistent with known sequelae of acetazolamide and TMZ. In the 23 WHO Grade 4 patients, the median overall survival (OS) was 30.1 months, and the median progression-free survival was 16.0 months. The 2-year OS was 60.9%. In total, 37% of the study population had high BCL-3 staining and trended toward shorter OS (17.2 months vs N.R., P=.06) (Riley et al., 2024) All of these factors will be evaluated in a prospective study including 60 patients Discussion/Significance of Impact: Initial data in a smaller cohort showed that adding acetazolamide is safe and tolerable in GBM patients on standard temozolomide. Survival compares favorably to historical data in MGMT-methylated GBM. BCL-3 may be a prognostic biomarker. These findings will be assessed and discussed in a 60-patient prospective study.
Hemmesi et al. (Wed,) studied this question.