Hematological toxicities in PARP inhibitors: A real-world study using FDA adverse event reporting system (FAERS) database

Objective Poly ADP-ribose polymerase inhibitors (PARPis) have significantly improved clinical effects in gynecological oncology. However, PARPis could also induce severe organ system toxicities, including the hematological system. Our study aimed to extensively characterize the hematological toxicities of PARPis based on the real-world data. Methods Disproportionality analysis was used to evaluate the association between PARPis and hematotoxicity adverse events. Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database between January 2015 and September 2021. The characteristics of PARPi-associated hematological toxicities, and the onset time and fatality proportion were further analyzed. Results Out of 24,045 adverse events reports, 4088 hematotoxicity reports (17.00%) were analyzed, with a median age of 64.95 (interquartile range [IQR] 51-71) years. All PARPis were detected with positive safety signals of hematological toxicities in four detection methods. Unexpected significant adverse events such as lymphadenopathy, lymphoedema, and metastases to lymph nodes might also occur. The median time-to-onset was 28 (IQR 10-101) days and the fatality proportion of hematological toxicities with PARPis was 8.76%, with a statistical difference in different PARPis. Conclusion Hematological toxicities caused by PARPis preferred to occur early and might result in serious outcomes. Early identification and response to the PARPi-related hematological toxicities were important and further basic research were needed to confirm the mechanism of results in this study.