Which tyrosine-kinase inhibitor to use first in chronic phase chronic myelogenous leukemia?

Abstract

Introduction: Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder distinctly characterized by the presence of the Philadelphia chromosome, which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22)]. The resulting translocation leads to the development of the BCR-ABL1 oncogene, a constitutively active fusion protein, which leads to uncontrolled cell proliferation and reduced apoptosis and has a clear association with driving the malignant activity of CML cells.

Areas covered: Given that the BCR-ABL1 oncogene is a known key cause of CML, it has led to the development of numerous small molecule tyrosine-kinase inhibitors (TKIs), which target the specific oncogene mutation in CML. Presently, there are three FDA-approved TKI agents, imatinib, dasatinib and nilotinib, for the treatment of frontline CML. Herein, we review the frontline options for the management of patients with CML and how to best choose these agents.

Expert opinion: Imatinib, dasatinib and nilotinib are all effective at yielding hematological, molecular and cytogenetic responses in patients with newly diagnosed CML. Frontline therapy may depend on physician experience, patient age and ability to tolerate therapy, and with the lack of data comparing all three agents alongside each other, imatinib, dasatinib, or nilotinib may all be suitable frontline choices.

Keywords:

• chronic myeloid leukemia
• dasatinib
• imatinib
• nilotinib
• tyrosine-kinase inhibitors

Declaration of interest

E Jabbour has received consulting fees from Bristol Meyers Squibb, Ariad, Teva, and Pfizer; he has also received research grants from GlaxoSmithKline/Novartis and Teva. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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