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Br J Clin Pharmacol. 2019 Oct;85(10):2280-2291. doi: 10.1111/bcp.13933. Epub 2019 May 23.

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

Author information

1
Pharmaceutical Sciences Postgraduate Programme, Universidade Federal do Paraná, Curitiba, Brazil.
2
Pharmacy Service, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
3
Research Institute for Medicines (iMed.ULisboa), Department of Social Pharmacy, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
4
Department of Pharmacy, Universidade Federal do Paraná, Curitiba, Brazil.

Abstract

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.

KEYWORDS:

chronic myeloid leukaemia; drug-related side effects and adverse reactions; network meta-analysis; tyrosine kinase inhibitors

PMID:
30907446
PMCID:
PMC6783623
[Available on 2020-10-01]
DOI:
10.1111/bcp.13933

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