A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System Events for Tazemetostat.

Abstract

Background: Tazemetostat, an EZH2 inhibitor approved for select sarcomas and lymphomas, has limited post-marketing safety data despite growing clinical use. This study aimed to evaluate the real-world safety profile of tazemetostat using data from the FDA Adverse Event Reporting System (FAERS) between Q1 2020 and Q4 2024.

Methods: Reports listing tazemetostat as the primary suspect drug were extracted, deduplicated, and analyzed using four disproportionality methods. Preferred Terms (PTs) were standardized via MedDRA 26.1 and mapped to System Organ Classes (SOCs). Subgroup analyses and time-to-onset assessments were performed across age, sex, and reporter types.

Results: A total of 1,179 adverse event reports associated with tazemetostat were retrieved from FAERS. Disproportionality analysis revealed significant signals across gastrointestinal, hematologic, and general systemic domains. Fatigue, nausea, decreased appetite, and anemia were the most commonly reported events. Significantly, taste disorder and somnolence were identified as new signals that were not present in FDA labeling. Most events occurred within the first 60 days of treatment, with similar onset patterns across demographic subgroups.

Conclusion: This FAERS-based analysis confirmed known toxicities and identified novel signals associated with tazemetostat in routine clinical use. These findings underscore the importance of continued pharmacovigilance to detect emerging adverse events and inform real-world monitoring strategies.

Clinical trial number: Not applicable.