Résumé

Tyrosine kinase inhibitors targeting BCR-ABL have been a real revolution in the treatment of chronic myeloid leukaemia, greatly improving surrogate outcomes and overall survival. However, new generation BCR-ABL tyrosine kinase inhibitors have recently been associated with occurrence of cardiovascular events. Indeed, during ponatinib clinical development, a high rate of patients with chronic myeloid leukaemia developed a vascular occlusive event. Retrospective analyses also demonstrated an increased incidence of similar events with nilotinib. Recently, a meta-analysis of randomised clinical trials confirmed this risk with nilotinib and ponatinib, but also identified dasatinib at higher risk of cardiovascular events than imatinib. Sub-analysis of this meta-analysis and retrospective studies indicated predominance of arterial events rather than venous. The number of patients treated with dasatinib and nilotinib has considerably increased since they have been
approved in first-line indication for patients with chronic-phase chronic myeloid leukaemia. In this context, the evaluation of the benefit-risk profile of these treatments is important, and implementation of measures to minimise the onset of cardiovascular events are required. They should include the selection of patients treated with new generation tyrosine kinase inhibitors, the monitoring of cardiovascular events and risk factors during treatment, and if required, the treatment of cardiovascular comorbidities. The pathophysiology of these events is probably multifactorial. Numerous hypotheses have already been advanced and suggest a worsening of the metabolic syndrome, an increase of atherosclerosis development and an impact of new generation tyrosine kinase inhibitors on off-targets related to vascular function.
langue originaleAnglais
Pages (de - à)45-52
Nombre de pages8
journalBelgian Journal of Hematology Volume
Volume8
Numéro de publication2
étatPublié - mars 2017

Empreinte digitale

Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Blood Vessels
Safety
Meta-Analysis
Leukemia, Myeloid, Chronic Phase
Therapeutics
Patient Selection
Comorbidity
Atherosclerosis
Randomized Controlled Trials
Retrospective Studies
Survival
Incidence
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Dasatinib
ponatinib

Citer ceci

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title = "Vascular safety profile of new generation BCR-ABL tyrosine kinase inhibitors in the treatment of chronic myeloid leukaemia",
abstract = "Tyrosine kinase inhibitors targeting BCR-ABL have been a real revolution in the treatment of chronic myeloid leukaemia, greatly improving surrogate outcomes and overall survival. However, new generation BCR-ABL tyrosine kinase inhibitors have recently been associated with occurrence of cardiovascular events. Indeed, during ponatinib clinical development, a high rate of patients with chronic myeloid leukaemia developed a vascular occlusive event. Retrospective analyses also demonstrated an increased incidence of similar events with nilotinib. Recently, a meta-analysis of randomised clinical trials confirmed this risk with nilotinib and ponatinib, but also identified dasatinib at higher risk of cardiovascular events than imatinib. Sub-analysis of this meta-analysis and retrospective studies indicated predominance of arterial events rather than venous. The number of patients treated with dasatinib and nilotinib has considerably increased since they have beenapproved in first-line indication for patients with chronic-phase chronic myeloid leukaemia. In this context, the evaluation of the benefit-risk profile of these treatments is important, and implementation of measures to minimise the onset of cardiovascular events are required. They should include the selection of patients treated with new generation tyrosine kinase inhibitors, the monitoring of cardiovascular events and risk factors during treatment, and if required, the treatment of cardiovascular comorbidities. The pathophysiology of these events is probably multifactorial. Numerous hypotheses have already been advanced and suggest a worsening of the metabolic syndrome, an increase of atherosclerosis development and an impact of new generation tyrosine kinase inhibitors on off-targets related to vascular function.",
keywords = "arterial occlusive disease, BCR-ABL positive, chronic, leukaemia, myelogenous, protein kinase inhibitors, review, venous thrombosis",
author = "H{\'e}l{\`e}ne Haguet and Jonathan Douxfils and Fran{\cc}ois Mullier and Christian Chatelain and Carlos Graux and Jean-Michel Dogne",
year = "2017",
month = "3",
language = "English",
volume = "8",
pages = "45--52",
journal = "Belgian Journal of Hematology Volume",
issn = "2033-3749",
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TY - JOUR

T1 - Vascular safety profile of new generation BCR-ABL tyrosine kinase inhibitors in the treatment of chronic myeloid leukaemia

AU - Haguet, Hélène

AU - Douxfils, Jonathan

AU - Mullier, François

AU - Chatelain, Christian

AU - Graux, Carlos

AU - Dogne, Jean-Michel

PY - 2017/3

Y1 - 2017/3

N2 - Tyrosine kinase inhibitors targeting BCR-ABL have been a real revolution in the treatment of chronic myeloid leukaemia, greatly improving surrogate outcomes and overall survival. However, new generation BCR-ABL tyrosine kinase inhibitors have recently been associated with occurrence of cardiovascular events. Indeed, during ponatinib clinical development, a high rate of patients with chronic myeloid leukaemia developed a vascular occlusive event. Retrospective analyses also demonstrated an increased incidence of similar events with nilotinib. Recently, a meta-analysis of randomised clinical trials confirmed this risk with nilotinib and ponatinib, but also identified dasatinib at higher risk of cardiovascular events than imatinib. Sub-analysis of this meta-analysis and retrospective studies indicated predominance of arterial events rather than venous. The number of patients treated with dasatinib and nilotinib has considerably increased since they have beenapproved in first-line indication for patients with chronic-phase chronic myeloid leukaemia. In this context, the evaluation of the benefit-risk profile of these treatments is important, and implementation of measures to minimise the onset of cardiovascular events are required. They should include the selection of patients treated with new generation tyrosine kinase inhibitors, the monitoring of cardiovascular events and risk factors during treatment, and if required, the treatment of cardiovascular comorbidities. The pathophysiology of these events is probably multifactorial. Numerous hypotheses have already been advanced and suggest a worsening of the metabolic syndrome, an increase of atherosclerosis development and an impact of new generation tyrosine kinase inhibitors on off-targets related to vascular function.

AB - Tyrosine kinase inhibitors targeting BCR-ABL have been a real revolution in the treatment of chronic myeloid leukaemia, greatly improving surrogate outcomes and overall survival. However, new generation BCR-ABL tyrosine kinase inhibitors have recently been associated with occurrence of cardiovascular events. Indeed, during ponatinib clinical development, a high rate of patients with chronic myeloid leukaemia developed a vascular occlusive event. Retrospective analyses also demonstrated an increased incidence of similar events with nilotinib. Recently, a meta-analysis of randomised clinical trials confirmed this risk with nilotinib and ponatinib, but also identified dasatinib at higher risk of cardiovascular events than imatinib. Sub-analysis of this meta-analysis and retrospective studies indicated predominance of arterial events rather than venous. The number of patients treated with dasatinib and nilotinib has considerably increased since they have beenapproved in first-line indication for patients with chronic-phase chronic myeloid leukaemia. In this context, the evaluation of the benefit-risk profile of these treatments is important, and implementation of measures to minimise the onset of cardiovascular events are required. They should include the selection of patients treated with new generation tyrosine kinase inhibitors, the monitoring of cardiovascular events and risk factors during treatment, and if required, the treatment of cardiovascular comorbidities. The pathophysiology of these events is probably multifactorial. Numerous hypotheses have already been advanced and suggest a worsening of the metabolic syndrome, an increase of atherosclerosis development and an impact of new generation tyrosine kinase inhibitors on off-targets related to vascular function.

KW - arterial occlusive disease

KW - BCR-ABL positive

KW - chronic

KW - leukaemia

KW - myelogenous

KW - protein kinase inhibitors

KW - review

KW - venous thrombosis

M3 - Article

VL - 8

SP - 45

EP - 52

JO - Belgian Journal of Hematology Volume

JF - Belgian Journal of Hematology Volume

SN - 2033-3749

IS - 2

ER -