Safety of venetoclax in real-world experience: data from the French national database of pharmacovigilance through all indications in hematological malignancies over 5 years

Background: Venetoclax is the first representative of a new class of targeted therapy, that inhibits selectively B-cell lymphoma-2 (BCL-2), an anti-apoptotic protein, frequently overexpressed in hematological malignancies. Venetoclax was approved by the Food and Drug Administration for chronic lymphocytic leukemia and for acute myeloid leukemia in 2016 and 2021, respectively. Because of its promising role in many hematological malignancies, several clinical trials are in progress and other extensions of indication are expected. An analysis of its long-term safety profile in real life is necessary. Objectives: The aim of our study was to evaluate all adverse events (AEs) reported to the French national pharmacovigilance database since its approval in France. Methods: We performed a retrospective study of all cases of AEs occurring under venetoclax recorded in the French national pharmacovigilance database since its market approval until March 2022 in France. Results: During the period study, a total of 209 AEs were spontaneously reported in 123 patients, of which 173 (82%) were serious. We confirmed that the most frequent toxicities described by the summary of product characteristic (SPC) and literature data on it, including hematological (21%), gastrointestinal (11%), dermatological (9%), infectious (8%) AEs, and tumor lysis syndrome (3%). Seventy-six (36%) AEs were not listed in the SPC for which the causal relationship of venetoclax could not be excluded including autoimmune hemolytic anemias (2%) or cardiac AEs (7%). Conclusion: These data especially in cardiac events provide important information on the safety of the venetoclax in a real-world setting.