Targeted therapy for patients with chronic myeloid leukemia: clinical trial experience and challenges in inter-trial comparisons

Abstract

The treatment of chronic myeloid leukemia (CML) was revolutionized by the introduction of the targeted tyrosine kinase inhibitor (TKI) imatinib mesylate. Later, to improve efficacy and tolerability, the more potent TKIs dasatinib and nilotinib were evaluated in CML. Clinicians comparing the clinical efficacy of TKIs face considerable challenges, including the variable treatment histories of patients receiving second-line therapy. The aim of this review is to highlight the pitfalls and possible solutions for comparing efficacy across disparate CML trials. Comparison of efficacy across trials is aided by careful consideration of possible confounding factors, including treatment history, definitions of imatinib intolerance or resistance, and BCR–ABL mutational status at baseline. However, methods exist to improve the comparability of data from different trials, yielding a more clinically and statistically meaningful inter-trial comparison.

Keywords::

• Imatinib mesylate
• nilotinib
• dasatinib
• chronic myeloid leukemia (CML)
• clinical trial
• tyrosine kinase inhibitor

Acknowledgements

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Nathalie Archer, MD, and Patricia Segarini, PhD, of Percolation Communications LLC for their medical editorial assistance.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.