Tagraxofusp, a first-in-class CD123-targeted anticancer agent: A pharmacovigilance study based on the FAERS database

Background: Tagraxofusp is a targeted therapy for blastic plasmacytoid dendritic cell neoplasm (BPDCN) that works by targeting cluster of differentiation 123 (CD123). It was the first drug approved by the FDA for this disease, and also represents the world's first approved CD123-targeting agent. However, existing evidence regarding the safety of tagraxofusp is primarily derived from clinical trials, which limits the ability to provide timely updates on associated adverse events(AEs). Aim: By using the FAERS database, we aim to mine and systematically describe AEs related to tagraxofusp from January 2019 to March 2025. Methods: All statistics were extracted from FAERS by four disproportional methods, which were reporting odds ratio, proportional reporting ratio, information component and empirical Bayes geometric mean. These four methods were perfomed to detect risk signals in the FAERS database to identify potential associations between tagraxofusp and AEs. Results: A total of 492 adverse event reports with tagraxofuspas the “primary suspect” were collected. A total of 1099 preferred terms and 22 system organ categories were obtained. The highest incidence of populations related to AEs was 26.2% in the 18-65 age group. Notably, Capillary Leak Syndrome (n = 92, reporting odds ratio 3457.54, proportional reporting ratio 2646.31, information component 11.29, empirical Bayes geometric mean 2506.77) exhibited the highest incidence and signal intensity. In addition, uncommon, but apparently strong adverse event signals were observed, such as blastic plasmacytoid dendritic cell neoplasia (n = 4, reporting odds ratio 2866.17, proportional reporting ratio 2836,93, information component 11.39, empirical Bayes geometric mean 2677.16), leukaemia recurrent(n = 8, reporting odds ratio 248.42, proportional reporting ratio 243.37, information component 7.92, empirical Bayes geometric mean 242.14),neoplasm recurrence(n = 13, reporting odds ratio 208.29, proportional reporting ratio 201.42, information component 7.65, empirical Bayes geometric mean 200.57) and blood albumin decreased(n = 23, reporting odds ratio 160.86, proportional reporting ratio 151.48, information component 7.24, empirical Bayes geometric mean 151.01). Multiple Organ Dysfunction Syndrome(n = 6, reporting odds ratio 12.56, proportional reporting ratio 12.38, information component 3.63, empirical Bayes geometric mean 12.38) also showed strong adverse event signals, which was not included in the instructions. Conclusion: In the clinical application of tagraxofusp, AEs with high signal strength should be closely monitored. At the same time, healthcare professionals should remain vigilant for the emergence of adverse event signals not described in the prescribing information and take appropriate preventive measures to ensure patient safety.