Recommendations for the Management of CML in the Era of Second-Generation TKIs

Abstract

Although imatinib 400 mg per day still represents the basic treatment for chronic myeloid leukemia (CML), the introduction of the second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib and their subsequent registration as potential first- or second-line therapies are offering more options for the treatment of the CML patients. With respect to imatinib, nilotinib and dasatinib appear to offer some advantages in terms of efficacy as first-line treatment for newly diagnosed CML patients, like the capacity to induce very fast and deep molecular responses (MR4 and MR4.5) as well as to prevent part of the early progressions to AP/BC that may occur during the first two–three years from diagnosis. However their use has been associated with increased long-term toxicity, in particular in some groups of patients, and their high cost may represent a limitation to their use in countries where generic imatinib is or will soon become available. Potential long-term toxicity and a higher cost with respect to imatinib are also the factors that may influence the decision of the clinicians to switch the therapy to the use of a second-generation TKI in the cases showing a nonoptimal response to imatinib. All these elements are now animating an intense debate among hematologists on which could be the best therapeutic options to be used as first- and/or second-line therapies in the clinical management of CML patients.