Risk assessment of cardiovascular adverse events with BTK inhibitors in hematological malignancies: Insights from FAERS.

12145 Background: Burton tyrosine Kinase inhibitors (BTKi) have revolutionized the care of chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHL) – including relapsed/refractory mantle cell, ABC diffuse large B cell lymphoma and and lymphoplasmacytic lymphoma. Ibrutinib was the first BTKi to be approved. The newer covalent BTKi include acalabrutinib and zanubrutinib, both of which are approved for frontline and relapsed CLL as well as relapsed NHL. All these agents have cardiovascular adverse events. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of different approved BTKi in the CLL as cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We analyzed cardiovascular events in 86,370 patients on BTKi. Cardiovascular event reports were submitted to FAERS between 2004-2023 and analyzed using the AERS Mine framework. We compared these incidences within different BTKI. We divided cardiovascular events to three categories: cardiac arrythmia, major coronary or vascular event (MACE) and pericardial complication including effusion or hemorrhage. Our primary composite endpoint was the PV of cardiovascular events caused by BTKI. To mitigate confounding, BTKI were analyzed as mutually exclusive cohorts: Ibrutinib (n = 79,278), acalabrutinib (5200), and zanubrutinib (1354). Two-way ANOVA testing was done to evaluate for statistical significance across the different groups. Results: Across the 86,370 patients on BTKI, we identified 8500 reports of cardiovascular events – ibrutinib (10.15%), acalabrutinib (5.73%), and Zanubrutinib (4.72%). Arrythmia risk was higher with ibrutinib (6.6%) compared to acalabrutinib (3.12%) and zanubrutinib (2.29%). The major difference in the groups was driven by atrial fibrillation (5.1% vs 2.1% vs 1.8%). The MACE rate was 2.79% vs. 2.4% vs. 2%, and pericardial events were 0.72% vs. 0.21% vs. 0.44% in the ibrutinib, acalabrutinib, and zanubrutinib groups, respectively. All the AEs were to have statistical significance (p = 0.011) across all the BTKI as mentioned in table 1. Conclusions: We report the prevalence rate of BTKI-related cardiovascular events in a large cohort of patients. Ibrutinib has demonstrated a higher incidence of toxicity, especially in cardiac arrythmias, while smaller but significant differences exist in other toxicities, including major cardiovascular events and pericardial effusion or hemorrhage. Patient selection and toxicity monitoring are important aspects of the care of these patients, who stay on these therapies for indefinite periods. Table: see text