(230) Tumor Lysis Syndrome Associated with Bruton's Tyrosine Kinase Inhibitor: A Disproportionality Analysis in a Spontaneous Reporting Database

Publication Number: 1275

Background: Bruton's tyrosine kinase inhibitors (BTKI) are used for treating B cell leukemias and lymphomas like Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, and Waldenström Macroglobulinemia. Tumor lysis syndrome (TLS) is an adverse event associated with this class, the prevalence of which is not well studied in a real-world context.

Objectives: To detect the possible safety signal of Bruton's tyrosine kinase inhibitor associated with tumor lysis syndrome through disproportionality analysis in the FDA Adverse Event Reporting System (FAERS) Database.

Methods: The 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 "Tumor lysis syndrome" and the drugs included in the analysis were Acalabrutinib, ibrutinib, and Zanubrutinib. Proportional reporting ratio (PRR) and Reporting odds ratio (ROR) was used as the analysis data mining algorithm. The threshold for a positive signal was considered as ROR- 1.96SE>1 and PRR>2 with an associated chi-square value of 4 or more.

Results: 2852 cases of TLS were identified from FAERS database, of which 121(4.2%) reports were associated with Bruton's tyrosine kinase inhibitor. Ibrutinib accounted for 103(85%), Acalabrutinib for 15(12%), and Zanubrutinib for 3(2.5%) cases of TLS reports associated with BTKI. The population's median age was 69(63-74) and 71(67-72) for Ibrutinib and Acalabrutinib, respectively. Positive signal strength was obtained for Ibrutinib [ROR 13.5(95%CI:11.1-16.4), PRR13.4(Chi-square:1131.11)], Acalabrutinib[ROR 42.8(25.7-71.3), PRR 42.3(560.93)] and Zanubrutinib [ROR 72.4(23-227.5) ,PRR 70.8(142.53)] associated TLS. On gender stratification, Acalabrutinib and Ibrutinib were found to have a higher value (ROR of 1.69 and 1.73 times, respectively) for females than males. Most of the cases were reported from the United States(n=101). Also, while stratifying the age groups, Acalabrutinib was seen to have a more significant influence on individuals from 65-100 (PRR 34.4), whereas Ibrutinib had more impact on the 45-64 age group (PRR 15.8). Most deaths(n=39) and life-threatening conditions(n=14) were seen in Ibrutinib group.

Conclusions: 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.