Single-center retrospective analysis of survival impact of acid sphingomyelinase inhibitors in glioblastoma

Acid sphingomyelinase (ASM) has been implicated in glioblastoma (GBM) lipid raft formation, which facilitates cancer signaling. A retrospective analysis of 203 GBM patients treated between 2015 and 2024 at Perlmutter Center of New York University evaluated the impact of ASM inhibitors (ASMi) on overall survival (OS). After adjusting for age, sex, tumor location, use of tumor-treating field, and MGMT promoter methylation status, ASMi use alone was not associated with a statistically significant OS benefit (HR 0.81; p=0.26). Stratifying by ASMi type revealed fluoxetine as the only agent that significantly improved OS (HR 0.36; p=0.03). In a fluoxetine-only multivariate analysis (n=17 versus 186 controls), the survival benefit remained significant (HR 0.38; p=0.04); this effect persisted in the adjusted propensity-matched cohort (HR 0.20; p=0.02). The authors conclude that fluoxetine was associated with increased survival in GBM patients.