Abstract
Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukemia (CML), can be associated to cardiovascular (CV) adverse events (AEs). A case/non-case study was performed using AE reports registered in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to compare the risk of CV event reports related to TKIs indicated in the management of chronic myeloid leukemia (CML). Disproportionality of CV event-related TKIs was computed using the Reporting Odds Ratio (ROR) as a measure of potential risk increase. Nilotinib accounts for more than half of reported cases related to TKIs. Signal of Disproportionate Reporting (SDR) was found for cardiac failure, ischemic heart disease, cardiac arrhythmias, torsade de pointes/QT prolongation, hypertension, and pulmonary hypertension. Dasatinib and bosutinib were related to the highest disproportionality for cardiac failure. Nilotinib was associated with the highest SDR for ischemic heart disease, torsade de pointes/QT prolongation and cardiac arrhythmias. Only ponatinib was related to an SDR for hypertension, while dasatinib and imatinib were related to pulmonary hypertension. In the context of CML, TKIs have different safety profiles related to CV events, among which nilotinib seems particularly related to. These results claim for a revision of its CV safety profile mainly for the risk of torsade de pointes/QT prolongation.
Highlights
Chronic myeloid leukemia (CML) is a malignant disease of haemopoietic stem cells with high incidence (1–2 cases per 100,000 adults) without any major geographic or ethnic difference [1]
The aim of this study was to compare the risk of reporting CV events in patients treated with Tyrosine kinase inhibitors (TKIs) indicated in the management of chronic myeloid leukemia (CML), and to describe the clinical characteristics of the involved patients
Among the 20,204,802 reports recorded in FAERS in the study period, a total of 1,306,242 adverse events (AEs) reports were related to anticancer drugs
Summary
Chronic myeloid leukemia (CML) is a malignant disease of haemopoietic stem cells with high incidence (1–2 cases per 100,000 adults) without any major geographic or ethnic difference [1]. The prevalence of CML is steadily rising due to the substantial prolongation of survival that has been achieved with targeted therapy [2]. CML arises from a chromosomal translocation causing a shortened chromosome 22 designated as the Philadelphia chromosome. This translocation leads to a fusion of the ABL1 and BCR genes that codes for the BCR-ABL1 protein characterized by high tyrosine kinase activity [3]. Efforts were aimed at developing compounds that could selectively inhibit the aberrant tyrosine kinase resulting from this molecular rearrangement
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