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. 2020 Mar 30;12(4):826.
doi: 10.3390/cancers12040826.

Cardiovascular Toxicity of Tyrosine Kinase Inhibitors Used in Chronic Myeloid Leukemia: An Analysis of the FDA Adverse Event Reporting System Database (FAERS)

Santa Cirmi  1   2 , Asmae El Abd  2 , Louis Letinier  2   3 , Michele Navarra  1 , Francesco Salvo  2   3
Affiliations

Cardiovascular Toxicity of Tyrosine Kinase Inhibitors Used in Chronic Myeloid Leukemia: An Analysis of the FDA Adverse Event Reporting System Database (FAERS)

Santa Cirmi et al. Cancers (Basel). .

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.

Keywords: FAERS; adverse drug reaction; cardiovascular toxicity; chronic myeloid leukemia; tyrosine kinase inhibitors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Forest plots of disproportionality (aROR) of TKIs and cardiovascular events.
Figure 2
Figure 2
Cumulative distribution function of TKIs by time-to-onset.
See this image and copyright information in PMC

References

    1. Jabbour E., Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am. J. Hematol. 2018;93:442–459. doi: 10.1002/ajh.25011. - DOI - PubMed
    1. Bower H., Bjorkholm M., Dickman P.W., Hoglund M., Lambert P.C., Andersson T.M. Life Expectancy of Patients with Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population. J. Clin. Oncol. 2016;34:2851–2857. doi: 10.1200/JCO.2015.66.2866. - DOI - PubMed
    1. Hochhaus A., Saussele S., Rosti G., Mahon F.X., Janssen J., Hjorth-Hansen H., Richter J., Buske C., Committee E.G. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2017;28(Suppl. 4):iv41–iv51. doi: 10.1093/annonc/mdx219. - DOI - PubMed
    1. Baccarani M., Deininger M.W., Rosti G., Hochhaus A., Soverini S., Apperley J.F., Cervantes F., Clark R.E., Cortes J.E., Guilhot F., et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872–884. doi: 10.1182/blood-2013-05-501569. - DOI - PMC - PubMed
    1. Larson R.A., Hochhaus A., Hughes T.P., Clark R.E., Etienne G., Kim D.W., Flinn I.W., Kurokawa M., Moiraghi B., Yu R., et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia. 2012;26:2197–2203. doi: 10.1038/leu.2012.134. - DOI - PubMed

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