Does the BCL-2 Inhibitor Venetoclax Increase the Risk of Cancer?A Real-World Pharmacovigilance Study

Abstract ID 100272 Poster Board 016 Venetoclax (VCX) is a novel BCL-2 inhibitor approved by the FDA for treating leukemia and Lymphoma. A recent study from our research laboratory has unexpectedly demonstrated that inhibition of BCL-2 in mice by VCX increased luminal progenitor-like cells in human breast cancer cell lines, disrupting mammary gland branching and inducing the epithelial-mesenchymal transition in mammary epithelial cells, a carcinogenesis marker. However, the long-term safety of VCX in a large sample population was not investigated. Thus, the primary purpose of the current study was to investigate the incidence of VCX-induced cancer as an adverse drug reaction. For this purpose, OpenVigil 2.1-MedDRA-v24 was used to search and extract the FDA Adverse Event Reporting System (FAERS) pharmacovigilance data on VCX from 2004Q1 to 2023Q1. The Disproportionality analysis (DPA) was then performed by OpenVigil 2 on every cancer adverse event at the Preferred Term (PT) level to analyze the association between VCX exposure and the cancer adverse event. The Disproportionality analysis (DPA) was then performed by OpenVigil 2 on every cancer adverse event at the Preferred Term (PT) level to examine the association between VCX use and the cancer adverse event. Our results showed that out of the fifteen cancer types, leukemias (1565, 6.8%), lymphomas (301, 1.3%), skin cancer (156, 0.7%), and sarcomas (15, 0.07%), were found to satisfy Evan's criteria and constitute adverse drug reactions (ADRs) due to VCX. The most common leukemias reported were acute myeloid leukemia (AML) (658, 2.8%) and chronic lymphocytic leukemia (CLL) (311, 1.36%), with males accounting for more than 50% of all cases across all age groups. Furthermore, VCX was identified as the primary suspect in 82% of all AML cases. In terms of the outcomes, death was the most common in both males and females, accounting for 74.6 % of all cases, with hospitalization coming in second (22.4 %). Finally, according to the current pharmacovigilance study, chronic VCX use causes carcinogenesis in multiple organs. These findings also raise concerns about VCX safety and send a message to healthcare providers about the possibility of VCX-induced cancer. The study was supported by Qatar University Internal Grant Nos. IRCC-2022-484 and QUCG-CPH-23/24-154.