Disproportionality Analysis of Tumour Lysis Syndrome (TLS) Associated with Bruton's Tyrosine Kinase Inhibitor (BTKi) using Food and Drug Administration Adverse Events Reporting System (FAERS) Database

Abstract

Abstract Background: Bruton's tyrosine kinase inhibitors (BTKis) are used for treating B-cell leukaemia and lymphomas like chronic lymphocytic leukaemia, mantle cell lymphoma, and Waldenström macroglobulinemia. Tumour lysis syndrome (TLS) is an adverse event associated with this class, the prevalence of which is not well studied in an actual context. Objective: This study aims to detect the possible safety signal of BTKis-associated with TLS through disproportionality analysis in the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Patients and Methods: A case/non-case retrospective disproportionality analysis was performed in a publicly available FAERS database using OpenVigil 2.1 (2014Q1-2021Q3). The preferred term defined by MedDRA v24 used for the study was "tumour lysis syndrome" and the drugs included in the analysis were acalabrutinib, ibrutinib, and zanubrutinib. Reporting odds ratio (ROR) was used as the analysis data mining algorithm. Results: 2852 cases of TLS were identified from FAERS database, of which 121 (4.2%) reports were associated with BTKis. Ibrutinib accounted for 103 (85.1%), acalabrutinib for 15 (12.4%), and zanubrutinib for 3 (2.5%) cases of TLS reports associated with BTKis. Positive signal strength was obtained for ibrutinib [ROR 13.5 (95%CI: 11.1-16.4), acalabrutinib [ROR 42.8 (25.7-71.3), and zanubrutinib [ROR 72.4 (23-227.5)] associated TLS. On gender stratification, acalabrutinib and ibrutinib were found to have a higher value (ROR of 1.7 times) for females than males. Conclusion: Our analysis of spontaneous reporting data identified signals for TLS with acalabrutinib, ibrutinib, and zanubrutinib. More research with a superior epidemiological study design of a defined population is required to validate these findings.