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. 2025 Jul 29:16:20406207251343116.
doi: 10.1177/20406207251343116. eCollection 2025.

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

Alexis Talbot  1 , Pierre-Edouard Debureaux  2 , Agnès Lillo-Le Louet  3   4 , Yasmine Derri  3   5 , Marine Aroux-Pavard  6 , Hélène Jantzem  7 , David M Smadja  3   5 , Cyrille Touzeau  8   9 , Christine Le Beller  3   4 , Nicolas Gendron  3   5
Affiliations

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

Alexis Talbot et al. Ther Adv Hematol. .

Abstract

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.

Keywords: acute myeloid leukemia; chronic lymphocytic leukemia; pharmacovigilance; real-world; safety; venetoclax.

Plain language summary

Understanding the safety of venetoclax: insights from 5 years of real-world data on blood cancer patients in France Background: Venetoclax is a new type of targeted therapy that blocks a specific protein (BCL-2), which helps cancer cells survive. This protein is often found in high levels in blood cancers. Venetoclax was approved for treating two types of blood cancers: chronic lymphocytic leukemia (CLL) in 2016 and acute myeloid leukemia (AML) in 2021. Since venetoclax is being tested in other blood cancers, it’s important to understand its long-term safety in real-world use, not just in clinical trials. Objectives: The goal of our study was to examine all the side effects (called adverse events or AEs) reported to the French national database that tracks medicine safety, since venetoclax became available in France. Methods: We looked back at all the cases of AEs in patients taking venetoclax that were reported to the French national pharmacovigilance database from when the drug was first approved up until March 2022. Results: In total, 209 AEs were reported for 123 patients, with 82% of these considered serious. The most common side effects were already known from clinical trials and official drug information: blood-related issues (21%), digestive problems (11%), skin reactions (9%), infections (8%), and a condition called tumor lysis syndrome (3%). However, 36% of the side effects had not been listed in the official drug information, including autoimmune blood disorders (2%) and heart-related issues (7%). Conclusion: This study offers valuable insights into the safety of venetoclax when used in everyday medical practice, helping doctors better understand the potential risks.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Flowchart of the study. AE, adverse event; FNPV, French national pharmacovigilance.
Figure 2.
Figure 2.
Number of adverse events related to venetoclax reported to the French pharmacovigilance network each year (a) and per patient (b). AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia.
Figure 3.
Figure 3.
Subanalysis of SOCs and AEs related to venetoclax reported to the French pharmacovigilance network. (a) Proportion of SOCs according to venetoclax indication; (b) proportion of SOCs according to venetoclax dose; (c) proportion of hematological AEs according to venetoclax indication. AE, adverse event; AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; SOC, system organ class.
See this image and copyright information in PMC

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