85
Views
20
CrossRef citations to date
0
Altmetric
Theme: General - Reviews

Tyrosine kinase inhibition: a therapeutic target for the management of chronic-phase chronic myeloid leukemia

, &
Pages 1433-1452 | Published online: 10 Jan 2014
 

Abstract

Chronic myeloid leukemia (CML) is a hematologic neoplasm with a progressive, ultimately terminal, disease course. In most cases, CML arises owing to the aberrant formation of a chimeric gene for a constitutively active tyrosine kinase. Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target, transforming the prognosis of patients with CML. New tyrosine kinase inhibitors continue to improve the management of CML, offering alternative options for those resistant to or intolerant of standard tyrosine kinase inhibitors. Here we review the pathobiology of CML and explore emerging strategies to optimize the management of chronic-phase CML, particularly first-line treatment.

Financial & competing interests disclosure

Dr Jabbour has received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, Ariad and Teva; Dr Cortes is a consultant for Ariad, Teva and Pfizer and has received grant support from Bristol-Myers Squibb, Novartis, Ariad, Teva and Pfizer; Dr Kantarjian has received research grants from Novartis, Bristol-Myers Squibb, Pfizer, Ariad and ChemGenex and is an unpaid consultant to Novartis. 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.

Medical writing support was provided by T Lonergan and J Ponting of Anthemis Consulting Ltd and was funded by Teva Pharmaceutical Industries, Frazer, PA, USA. Teva provided a single medical accuracy review of the final draft. The authors were not compensated and retained full editorial control over the content of the paper.

Key issues

  • • Tyrosine kinase inhibitors (TKIs) have transformed the management of chronic myeloid leukemia; however, a significant proportion of patients respond suboptimally or fail to respond to first-line TKIs.

  • • The optimal first-line treatment is unclear; long-term survival data for the different TKIs are lacking.

  • • Achieving complete cytogenetic response (CCyR) is the key goal of treatment; in patients with a CCyR, changing treatment in response to modest increases in BCR–ABL transcript levels may not be the optimal approach.

  • • Clinical evidence is currently lacking for the outcomes of switching TKI treatment. For patients who fail to achieve an early response, we need more information to guide decisions on when to switch and what to switch to.

  • • Physicians must be vigilant for treatment-related adverse effects that may emerge with long-term therapy.

  • • Non-TKI therapies, such as omacetaxine and PEG-IFN-α, also have a role in the management of chronic myeloid leukemia.

  • • Although there is some evidence that TKI therapy can be safely stopped in some patients who respond well, further investigation is required and at present stopping is not recommended in clinical practice.

Notes

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 99.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 786.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.