Abstract

Chronic myeloid leukemia (CML) accounts for one in five cases of leukemia in adults [1]. Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment paradigm for CML. The first, imatinib (Gleevec/Glivec), was approved in 2002 by the U.S. Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products. Although data on the long-term effectiveness of imatinib were sparse, early cost-effectiveness analyses based on conservative associations between short-term cytogenetic response and long-term quality-adjusted survival indicated that its use in chronic-phase disease was of good value, despite a cost of $29,000 per year in 2002 [2]. Consistent with these findings, guidance from the U.K. National Institute for Health and Clinical Excellence recommends the use of standard-dose imatinib (400 mg/d) as first-line therapy for chronic-phase CML [3].

Some patients do not respond to standard-dose imatinib (i.e., primary resistance), and some patients lose their response (i.e., secondary resistance). In the landmark International Randomized Study of Interferon and STI571, approximately one in four patients had primary resistance at 18 months [4]; by 5 years, one in four patients had developed secondary resistance [5]. Although stem cell transplant is an option, many patients are not appropriate candidates. Other options include interferon alfa and hydroxyurea/hydroxycarbamide, but increasing the dose of imatinib to 600 or 800 mg/d or switching to treatment with a second-generation TKI is considered to be more effective [6].