Venetoclax and Tumor Lysis Syndrome (TLS): Data Mining of the FDA Adverse Event Reporting System (FAERS) Database

• Published in: Drug safety Vol. 45; no. 10; pp. 1155 - 1156
• Main Authors: Giorgio, C D, Pascale, G, Cimarusti, C C, Corni, F, Drago, D, Napoli, L, Ingrillì, S, Ruggiero, F, Cervi, L
• Format: Journal Article
• Language: English
• Published: Auckland Springer Nature B.V 01.10.2022
• Subjects: Adverse events; Apoptosis; Bcl-2 protein; Chronic lymphocytic leukemia; Data mining; Drugs; Health services; Internet; Leukemia; Lymphocytes B; Lymphoma; Lysis; Medicine; Mimetic compounds; Patients; Pharmacovigilance; Risk; Tumors
• ISSN: 0114-5916; 1179-1942

Introduction: Venetoclax is a BH3-mimetic compound that selectively antagonizes BCL-2 (B-cell lymphoma 2) and induces apoptosis of CLL (Chronic Lymphocytic Leukemia) cells [1]. This oral treatment has demonstrated significant clinical advantages, but rapid tumor debulking can lead to a treatment-related risk of the acute condition known as tumor lysis syndrome (TLS), caused by the abrupt release of cellular components into the bloodstream [2]. A warning has been issued by the European Medicine Agency (EMA) and Italian Medicine Agency (AIFA) regarding the risk of TLS in patients treated with venetoclax [3]. Objective: The objective of this study was to investigate whether a disproportionally elevated signal of developing TLS may be detected in patients treated with venetoclax as compared to those treated with other drugs. Methods: A retrospective analysis of spontaneously reported cases of TLS contained in the free and publicly available FDA Adverse Event Reporting System (FAERS) database was conducted in the period January 2015-December 2020 [4]. We calculated, as a signal of disproportionality, the reporting odds ratio (ROR), and the relative 95% confidence interval (CI), of TLS in patients treated with venetoclax. The signal was considered significant when the ROR lower limit of the 95% CI was > 1. Results: A total of 11.800.647 FAERS reports were identified during the study period; 15.933 (0.13%) reports mentioned venetocalx. There were 2.978 (0.02%) reports of TLS of which 353 (11.8%) attributed to venetoclax treatment. The majority of these reports referred to patients aged 65-85 years (41%) and male (61.18%) (OR = 87.89, 95% CI 78.53-98.14, z = 78.72 P <0.0001) as compared to other drugs. Conclusion: With this study we demonstrated that in patients treated with venetoclax exists a higher risk to develop TLS. It would be of interest to further analyze reports of TLS associated with this drug, comparing signals deriving from FAERS and those deriving from the European pharmacovigilance database EudraVigilance [5]. EMA and AIFA has recommended a continuous and constant updating of information on venetoclax to reflect current knowledge on this issue and address it in the best possible way and in the shortest possible time.