Risk of arterial and venous occlusive events in chronic myeloid leukemia patients treated with new generation BCR-ABL tyrosine kinase inhibitors: A systematic review and meta-analysis.

Haguet, Hélène;Douxfils, Jonathan;Mullier, François;Chatelain, Christian;Dogné, Jean-Michel;et.al.
(2017) Expert Opinion on Drug Safety — Vol. 16, n° 1, p. 5-12 (2017)

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Authors
  • Haguet, Hélène
    Author
  • Douxfils, Jonathan
    Author
  • Mullier, FrançoisUCLouvain
    Author
  • Chatelain, ChristianUCLouvain
    Author
  • Graux, CarlosUCLouvain
    Author
  • Dogné, Jean-Michel
    Author
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Abstract
(en) BACKGROUND: A previous meta-analysis demonstrated that 3 of the new-generation BCR-ABL tyrosine kinase inhibitors (TKIs) (dasatinib, nilotinib and ponatinib) are associated with an increased risk of vascular occlusive events in patients with Ph+ chronic myeloid leukemia compared with imatinib. This meta-analysis of randomized controlled trials aims at assessing these risks separately. METHODS: The literature search was performed by two independent reviewers following the previous protocol (PROSPERO 2014:CRD42014014147). A random-effects model and a fixed-effect model were used according to the characteristics of the included studies. Peto odds ratios with 95%CI were computed. RESULTS: Overall, 4.78% of patients developed arterial occlusive events with new generation TKIs compared with 0.96% with imatinib. Ponatinib (ORPETO:3.26; 95%CI:1.12 to 9.50), nilotinib (ORPETO: 3.69; 95%CI:2.29 to 5.95) and dasatinib (ORPETO:3.32; 95%CI:1.37 to 8.01) are all associated with a higher risk of arterial occlusive events than imatinib. Venous occlusive events occur in 0.72% of patients treated with new generation TKIs and in 0.27% of imatinib-treated patients. Overall, a trend toward an increase of the rate of venous occlusive events with new-generation TKIs (ORPETO:2.17; 95%CI:0.90 to 5.25) was highlighted but stratifications by treatment gave nonsignificant results. CONCLUSIONS: Vascular occlusive events associated with new-generation BCR-ABL TKIs are driven by arterial occlusive events.
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Haguet, H., Douxfils, J., Mullier, F., Chatelain, C., Graux, C., & Dogné, J.-M. (2017). Risk of arterial and venous occlusive events in chronic myeloid leukemia patients treated with new generation BCR-ABL tyrosine kinase inhibitors: A systematic review and meta-analysis. Expert Opinion on Drug Safety, 16(1), 5-12. https://doi.org/10.1080/14740338.2017.1261824 (Original work published 2017)