Hélène Haguet1,2, Jonathan Douxfils1, François Mullier2, Christian Chatelain1, Carlos Graux3, Jean-Michel Dogné1. 1. a Department of Pharmacy , University of Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Namur , Belgium. 2. b Haematology Laboratory , Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Yvoir , Belgium. 3. c Department of Haematology , Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Yvoir , Belgium.
Abstract
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.
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.
Authors: Eric J Chow; David R Doody; Jennifer J Wilkes; Laura K Becker; Shasank Chennupati; Pamela E Morin; Lena E Winestone; Henry J Henk; Gary H Lyman Journal: Leuk Lymphoma Date: 2020-12-07
Authors: Steven P Grover; Yohei M Hisada; Raj S Kasthuri; Brandi N Reeves; Nigel Mackman Journal: Arterioscler Thromb Vasc Biol Date: 2021-02-11 Impact factor: 8.311