Abstract 10554: Major Cardiac Side Effects of BTK and BCR-ABL Kinase Inhibitor Therapy in Cancer Patients: A Global WHO Database Analysis

Abstract

Introduction: Bruton’s tyrosine kinase (BTK) and BCR-ABL kinase inhibitors have transformed the treatment for hematological cancers, such as mantle cell lymphoma and chronic myelogenous leukemia. However, these therapies present unique cardiac events that remain underexplored. Hypothesis: We hypothesize that the two groups of targeted therapies commonly used to treat hematological cancers will differ in cardiac side-effect profiles. Methods: The World Health Organization database, VigiBase ®, contains over 20 million Individual Case Safety Reports and is maintained by the Uppsala Monitoring Centre. Reports for unique cardiac events associated with the use of BTK and BCR-ABL kinase inhibitors were analyzed. Reporting odds ratios (ROR), 95% confidence intervals (CI) and chi-squared tests were used to compare differences in cardiac side-effect profiles between the two groups of therapies. Results: A total of 24,385 adverse cardiac events from the use of BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib) and BCR-ABL kinase inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) have been observed based on records obtained to-date. Compared to BCR-ABL kinase inhibitors, BTK inhibitors have significantly increased reporting for atrial fibrillation (ROR: 6.995; 95% CI: 6.493-7.537; P < 0.001) and ventricular tachycardia (ROR: 1.829; 95% CI: 1.342-2.493; P < 0.001). However, BCR-ABL inhibitors have significantly increased reporting for myocardial infarction (ROR: 2.077; 95% CI: 1.863-2.316; P < 0.001) but similar reporting for congestive cardiac failure (ROR: 0.949; 95% CI: 0.852-1.058; P = 0.343). The median onset of ventricular tachycardia from the use of BTK inhibitors is 176 days (interquartile range: 48-636 days). For BCR-ABL kinase inhibitors, the median onset of ventricular tachycardia is similar at 137 days (interquartile range: 92-396 days), P = 0.741 from nonparametric tests. Conclusion: We conclude that BTK inhibitors are associated with arrhythmic events, while BCR-ABL kinase inhibitors are associated with myocardial infarction. Both groups have similar reporting for congestive cardiac failure. Research is underway to study the mechanisms behind these novel side-effect profiles.