Imatinib mesylate for the treatment of chronic myeloid leukemia

Abstract

Chronic myeloid leukemia (CML) is the first human malignancy for which the promise of targeted therapy has come true. CML is invariably associated with a specific genetic lesion – the t(9;22) chromosomal translocation. As a consequence of this translocation, a BCR-ABL fusion gene is formed on the 22q- derivative (traditionally known as the Philadelphia chromosome) and the deregulated tyrosine kinase activity of the protein encoded by this gene has been shown to be both necessary and sufficient for initiation and maintenance of the disease. Imatinib mesylate, an orally available tyrosine kinase inhibitor that targets Bcr-Abl, entered clinical evaluation in 1998. Its efficacy surpassed almost everyone’s predictions, and the observation of high response rates and favorable toxicity profile associated with imatinib therapy led to its approval as first-line treatment for all newly diagnosed CML patients over an exceptionally short period of time. The 6-year results of the Phase III trial have recently been reported and confirm durability of responses and declining incidence of adverse events over time, although, at present, occurrence of unexpected side effects in the long term cannot be excluded. Although imatinib does not ‘cure’ CML and has to be administered chronically to patients, it has revolutionized both outcome and quality of life of CML patients.

Keywords::

• Bcr-Abl
• Philadelphia-positive leukemia
• targeted therapy
• tyrosine kinase inhibitor

Financial & competing interests disclosure

Michele Baccarani is a consultant for Novartis, Wyeth, Merck, Bristol-Myers Squibb, received research funding from Novartis, Wyeth and Bristol Myers Squibb, received honoraria from Novartis, Wyeth, Bristol-Myers Squibb, Merck and paid expert testimony information from Novartis, Wyeth and Bristol-Myers Squibb. Giovanni Martinelli has received research funding from Novartis and Merck. This work was supported by European LeukemiaNet, AIL, AIRC, PRIN projects and Fondazione del Monte di Bologna e Ravenna. 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.

No writing assistance was utilized in the production of this manuscript.