META-ANALYSIS OF THE RISKS OF ARTERIAL AND VENOUS OCCLUSIVE EVENTS WITH NEW GENERATION BCR-ABL TKIS IN PATIENTS WITH CHRONIC MYELOID LEUKAEMIA
(Abstract release date: 05/19/16)
EHA Library. Haguet H. 06/09/16; 132645; E1096
Disclosure(s): François Mullier reports personal fees from Boehringer Ingelheim, Bayer Healthcare and Bristol-Myers Squibb-Pfizer outside the submitted work. Carlos Graux reports personal fees from Novartis, Celgene, and Amgen, outside the submitted work. The other authors have no conflict of interest to disclose.
Mrs. Hélène Haguet
Contributions
Contributions
Abstract
Abstract: E1096
Type: Eposter Presentation
Background
A recent meta-analysis demonstrated that 3 of the new generation BCR-ABL tyrosine kinase inhibitors (TKIs) (i.e. dasatinib, nilotinib and ponatinib) are associated with an enhancement of major molecular response without improving the overall survival at one year in patients with PH+ chronic myeloid leukaemia (CML) compared with imatinib. This study also highlighted their association with an increased risk of vascular occlusive events compared with imatinib but distinction between arterial of venous events was not assessed.
Aims
To perform a meta-analysis on the risk of arterial and venous occlusive events in patients with Ph+ CML treated with new generation BCR-ABL TKIs in randomized clinical trials (RCTs).
Methods
The literature search (data lock point: November 26, 2015) was conducted according to a registered protocol (PROSPERO 2014:CRD42014014147). All RCTs comparing a new generation BCR-ABL TKI versus imatinib in patients with Ph+ CML were included. Two independent investigators were responsible of the screening, the review and the extraction of the data using standard forms. The meta-analysis was performed using a random (REM) and a fixed (FEM) effect model according to the characteristics of the included studies. ORs with 95% CIs were computed using the Peto method. Statistical heterogeneity was quantified using the I2 value, and publication bias was assessed by funnel plots.
Results
Among the 400 abstracts identified, 12 studies fulfilled the established criteria and were included in the statistical analysis. Overall, 4.47% (99/2,217) of patients developed arterial occlusive events with new generation BCR-ABL TKIs compared with 0.80% (15/1,884) with imatinib (REM ORPETO: 3.46; 95%CI: 2.35 to 5.10). Ponatinib (REM ORPETO: 3.26; 95%CI: 1.12 to 9.50), nilotinib (REM ORPETO: 3.60; 95%CI: 2.21 to 5.86) and dasatinib (REM ORPETO: 3.32; 95%CI: 1.37 to 8.01) are associated with higher risk of arterial occlusive events than imatinib. No significant difference was found with bosutinib. Venous occlusive events occur in only 0.86% (13/2,217) of patients treated with new generation TKIs and in 0.16% (3/1,884) of imatinib-treated patients. Overall, new generation TKIs increase the rate of venous occlusive events (REM ORPETO: 2.85; 95%CI: 1.04 to 7.78) but stratifications by treatment provided nonsignificant results. Funnel plots demonstrate no evidences of publication bias, and the I2 statistic specifies no heterogeneity among studies.Limitations of this meta-analysis include the absence of a time-to-event analysis and the inconsistent report of cardiovascular events in the literature. However, the use of a clinical trial register aimed to decrease this heterogeneity.
Conclusion
The increased risk of vascular occlusive events associated with new generation BCR-ABL TKIs is mainly driven by thrombotic events occurring at the arterial side. Additional investigations are required to assess the underlying pathophysiological mechanisms and provide appropriate risk minimization measures.
Session topic: E-poster
Keyword(s): Arterial thrombosis, Chronic myeloid leukemia, Tyrosine kinase inhibitor, Venous thromboembolism
Type: Eposter Presentation
Background
A recent meta-analysis demonstrated that 3 of the new generation BCR-ABL tyrosine kinase inhibitors (TKIs) (i.e. dasatinib, nilotinib and ponatinib) are associated with an enhancement of major molecular response without improving the overall survival at one year in patients with PH+ chronic myeloid leukaemia (CML) compared with imatinib. This study also highlighted their association with an increased risk of vascular occlusive events compared with imatinib but distinction between arterial of venous events was not assessed.
Aims
To perform a meta-analysis on the risk of arterial and venous occlusive events in patients with Ph+ CML treated with new generation BCR-ABL TKIs in randomized clinical trials (RCTs).
Methods
The literature search (data lock point: November 26, 2015) was conducted according to a registered protocol (PROSPERO 2014:CRD42014014147). All RCTs comparing a new generation BCR-ABL TKI versus imatinib in patients with Ph+ CML were included. Two independent investigators were responsible of the screening, the review and the extraction of the data using standard forms. The meta-analysis was performed using a random (REM) and a fixed (FEM) effect model according to the characteristics of the included studies. ORs with 95% CIs were computed using the Peto method. Statistical heterogeneity was quantified using the I2 value, and publication bias was assessed by funnel plots.
Results
Among the 400 abstracts identified, 12 studies fulfilled the established criteria and were included in the statistical analysis. Overall, 4.47% (99/2,217) of patients developed arterial occlusive events with new generation BCR-ABL TKIs compared with 0.80% (15/1,884) with imatinib (REM ORPETO: 3.46; 95%CI: 2.35 to 5.10). Ponatinib (REM ORPETO: 3.26; 95%CI: 1.12 to 9.50), nilotinib (REM ORPETO: 3.60; 95%CI: 2.21 to 5.86) and dasatinib (REM ORPETO: 3.32; 95%CI: 1.37 to 8.01) are associated with higher risk of arterial occlusive events than imatinib. No significant difference was found with bosutinib. Venous occlusive events occur in only 0.86% (13/2,217) of patients treated with new generation TKIs and in 0.16% (3/1,884) of imatinib-treated patients. Overall, new generation TKIs increase the rate of venous occlusive events (REM ORPETO: 2.85; 95%CI: 1.04 to 7.78) but stratifications by treatment provided nonsignificant results. Funnel plots demonstrate no evidences of publication bias, and the I2 statistic specifies no heterogeneity among studies.Limitations of this meta-analysis include the absence of a time-to-event analysis and the inconsistent report of cardiovascular events in the literature. However, the use of a clinical trial register aimed to decrease this heterogeneity.
Conclusion
The increased risk of vascular occlusive events associated with new generation BCR-ABL TKIs is mainly driven by thrombotic events occurring at the arterial side. Additional investigations are required to assess the underlying pathophysiological mechanisms and provide appropriate risk minimization measures.
Session topic: E-poster
Keyword(s): Arterial thrombosis, Chronic myeloid leukemia, Tyrosine kinase inhibitor, Venous thromboembolism
Abstract: E1096
Type: Eposter Presentation
Background
A recent meta-analysis demonstrated that 3 of the new generation BCR-ABL tyrosine kinase inhibitors (TKIs) (i.e. dasatinib, nilotinib and ponatinib) are associated with an enhancement of major molecular response without improving the overall survival at one year in patients with PH+ chronic myeloid leukaemia (CML) compared with imatinib. This study also highlighted their association with an increased risk of vascular occlusive events compared with imatinib but distinction between arterial of venous events was not assessed.
Aims
To perform a meta-analysis on the risk of arterial and venous occlusive events in patients with Ph+ CML treated with new generation BCR-ABL TKIs in randomized clinical trials (RCTs).
Methods
The literature search (data lock point: November 26, 2015) was conducted according to a registered protocol (PROSPERO 2014:CRD42014014147). All RCTs comparing a new generation BCR-ABL TKI versus imatinib in patients with Ph+ CML were included. Two independent investigators were responsible of the screening, the review and the extraction of the data using standard forms. The meta-analysis was performed using a random (REM) and a fixed (FEM) effect model according to the characteristics of the included studies. ORs with 95% CIs were computed using the Peto method. Statistical heterogeneity was quantified using the I2 value, and publication bias was assessed by funnel plots.
Results
Among the 400 abstracts identified, 12 studies fulfilled the established criteria and were included in the statistical analysis. Overall, 4.47% (99/2,217) of patients developed arterial occlusive events with new generation BCR-ABL TKIs compared with 0.80% (15/1,884) with imatinib (REM ORPETO: 3.46; 95%CI: 2.35 to 5.10). Ponatinib (REM ORPETO: 3.26; 95%CI: 1.12 to 9.50), nilotinib (REM ORPETO: 3.60; 95%CI: 2.21 to 5.86) and dasatinib (REM ORPETO: 3.32; 95%CI: 1.37 to 8.01) are associated with higher risk of arterial occlusive events than imatinib. No significant difference was found with bosutinib. Venous occlusive events occur in only 0.86% (13/2,217) of patients treated with new generation TKIs and in 0.16% (3/1,884) of imatinib-treated patients. Overall, new generation TKIs increase the rate of venous occlusive events (REM ORPETO: 2.85; 95%CI: 1.04 to 7.78) but stratifications by treatment provided nonsignificant results. Funnel plots demonstrate no evidences of publication bias, and the I2 statistic specifies no heterogeneity among studies.Limitations of this meta-analysis include the absence of a time-to-event analysis and the inconsistent report of cardiovascular events in the literature. However, the use of a clinical trial register aimed to decrease this heterogeneity.
Conclusion
The increased risk of vascular occlusive events associated with new generation BCR-ABL TKIs is mainly driven by thrombotic events occurring at the arterial side. Additional investigations are required to assess the underlying pathophysiological mechanisms and provide appropriate risk minimization measures.
Session topic: E-poster
Keyword(s): Arterial thrombosis, Chronic myeloid leukemia, Tyrosine kinase inhibitor, Venous thromboembolism
Type: Eposter Presentation
Background
A recent meta-analysis demonstrated that 3 of the new generation BCR-ABL tyrosine kinase inhibitors (TKIs) (i.e. dasatinib, nilotinib and ponatinib) are associated with an enhancement of major molecular response without improving the overall survival at one year in patients with PH+ chronic myeloid leukaemia (CML) compared with imatinib. This study also highlighted their association with an increased risk of vascular occlusive events compared with imatinib but distinction between arterial of venous events was not assessed.
Aims
To perform a meta-analysis on the risk of arterial and venous occlusive events in patients with Ph+ CML treated with new generation BCR-ABL TKIs in randomized clinical trials (RCTs).
Methods
The literature search (data lock point: November 26, 2015) was conducted according to a registered protocol (PROSPERO 2014:CRD42014014147). All RCTs comparing a new generation BCR-ABL TKI versus imatinib in patients with Ph+ CML were included. Two independent investigators were responsible of the screening, the review and the extraction of the data using standard forms. The meta-analysis was performed using a random (REM) and a fixed (FEM) effect model according to the characteristics of the included studies. ORs with 95% CIs were computed using the Peto method. Statistical heterogeneity was quantified using the I2 value, and publication bias was assessed by funnel plots.
Results
Among the 400 abstracts identified, 12 studies fulfilled the established criteria and were included in the statistical analysis. Overall, 4.47% (99/2,217) of patients developed arterial occlusive events with new generation BCR-ABL TKIs compared with 0.80% (15/1,884) with imatinib (REM ORPETO: 3.46; 95%CI: 2.35 to 5.10). Ponatinib (REM ORPETO: 3.26; 95%CI: 1.12 to 9.50), nilotinib (REM ORPETO: 3.60; 95%CI: 2.21 to 5.86) and dasatinib (REM ORPETO: 3.32; 95%CI: 1.37 to 8.01) are associated with higher risk of arterial occlusive events than imatinib. No significant difference was found with bosutinib. Venous occlusive events occur in only 0.86% (13/2,217) of patients treated with new generation TKIs and in 0.16% (3/1,884) of imatinib-treated patients. Overall, new generation TKIs increase the rate of venous occlusive events (REM ORPETO: 2.85; 95%CI: 1.04 to 7.78) but stratifications by treatment provided nonsignificant results. Funnel plots demonstrate no evidences of publication bias, and the I2 statistic specifies no heterogeneity among studies.Limitations of this meta-analysis include the absence of a time-to-event analysis and the inconsistent report of cardiovascular events in the literature. However, the use of a clinical trial register aimed to decrease this heterogeneity.
Conclusion
The increased risk of vascular occlusive events associated with new generation BCR-ABL TKIs is mainly driven by thrombotic events occurring at the arterial side. Additional investigations are required to assess the underlying pathophysiological mechanisms and provide appropriate risk minimization measures.
Session topic: E-poster
Keyword(s): Arterial thrombosis, Chronic myeloid leukemia, Tyrosine kinase inhibitor, Venous thromboembolism
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