Haematological adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukaemia: A network meta-analysis

Fachi, MM; Tonin, FS; Leonart, LP; Rotta, I; Fernandez-Llimos, F; Pontarolo, R

Haematological adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukaemia: A network meta-analysis

Fachi, MM Tonin, FS Leonart, LP Rotta, I Fernandez-Llimos, F

Pontarolo, R

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Publication Type:: Journal Article
Citation:: British Journal of Clinical Pharmacology, 2019, 85 (10), pp. 2280 - 2291
Issue Date:: 2019-10-01

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Field	Value	Language
dc.contributor.author	Fachi, MM	en_US
dc.contributor.author	Tonin, FS	en_US
dc.contributor.author	Leonart, LP	en_US
dc.contributor.author	Rotta, I	en_US
dc.contributor.author	Fernandez-Llimos, F https://orcid.org/0000-0002-8529-9595	en_US
dc.contributor.author	Pontarolo, R	en_US
dc.date.available	2019-02-22	en_US
dc.date.issued	2019-10-01	en_US
dc.identifier.citation	British Journal of Clinical Pharmacology, 2019, 85 (10), pp. 2280 - 2291	en_US
dc.identifier.issn	0306-5251	en_US
dc.identifier.uri	http://hdl.handle.net/10453/137463
dc.description.abstract	© 2019 The British Pharmacological Society Aims: Despite their overall favourable safety profile, tyrosine kinase inhibitors (TKIs) are related to severe adverse events including haematological toxicities such as anaemia, leucopenia, neutropenia and thrombocytopenia. We designed a systematic review and network meta-analysis of randomised controlled trials to compare safety among TKIs (bosutinib, dasatinib, imatinib, nilotinib, ponatinib and radotinib) used by patients diagnosed with chronic myeloid leukaemia. Methods: We obtained data from the PubMed, Scopus, Web of Science, and SciELO databases. The Bayesian approach was used for direct and indirect comparisons, and the treatments were ranked by the surface under the cumulative ranking curve (SUCRA). Results: Seventeen studies were included in the network meta-analysis. Our data show that dasatinib was generally considered worse than the other TKIs, with SUCRA values for 140 mg dasatinib of 90.3% for anaemia, 87.4% for leucopenia, 90.6% for neutropenia and 97.2% for thrombocytopenia. In addition, nilotinib was shown to be safer, with SUCRA values for 600 and 800 mg doses of 21.9 and 35.8% for anaemia, 23.8 and 14.6% for leucopenia, 33.0 and 17.7% for neutropenia, and 28.7 and 32.6% for thrombocytopenia, respectively. Conclusion: Dasatinib appeared as the least safe drug for chronic myeloid leukaemia, probably because it binds to multiple key kinase targets, being more prone to cause serious haematological adverse events. Nilotinib demonstrated a safer profile, mostly due to its selective binding capacity.	en_US
dc.relation.ispartof	British Journal of Clinical Pharmacology	en_US
dc.relation.isbasedon	10.1111/bcp.13933	en_US
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.title	Haematological adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukaemia: A network meta-analysis	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	85	en_US
utslib.for	1112 Oncology and Carcinogenesis	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
utslib.copyright.status	closed_access
pubs.issue	10	en_US
pubs.publication-status	Published	en_US
pubs.volume	85	en_US

Abstract:

© 2019 The British Pharmacological Society Aims: Despite their overall favourable safety profile, tyrosine kinase inhibitors (TKIs) are related to severe adverse events including haematological toxicities such as anaemia, leucopenia, neutropenia and thrombocytopenia. We designed a systematic review and network meta-analysis of randomised controlled trials to compare safety among TKIs (bosutinib, dasatinib, imatinib, nilotinib, ponatinib and radotinib) used by patients diagnosed with chronic myeloid leukaemia. Methods: We obtained data from the PubMed, Scopus, Web of Science, and SciELO databases. The Bayesian approach was used for direct and indirect comparisons, and the treatments were ranked by the surface under the cumulative ranking curve (SUCRA). Results: Seventeen studies were included in the network meta-analysis. Our data show that dasatinib was generally considered worse than the other TKIs, with SUCRA values for 140 mg dasatinib of 90.3% for anaemia, 87.4% for leucopenia, 90.6% for neutropenia and 97.2% for thrombocytopenia. In addition, nilotinib was shown to be safer, with SUCRA values for 600 and 800 mg doses of 21.9 and 35.8% for anaemia, 23.8 and 14.6% for leucopenia, 33.0 and 17.7% for neutropenia, and 28.7 and 32.6% for thrombocytopenia, respectively. Conclusion: Dasatinib appeared as the least safe drug for chronic myeloid leukaemia, probably because it binds to multiple key kinase targets, being more prone to cause serious haematological adverse events. Nilotinib demonstrated a safer profile, mostly due to its selective binding capacity.

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http://hdl.handle.net/10453/137463