Haema 2012; 3(1): 23-36
by Constantinos Tsatalas, Emmanouil Spanoudakis, Ioannis Kotsianidis
Department of Haematology, Democritous University of Thrace Medical School, Alexandroupolis
Abstract
The clinical outcome for patients with CP-CML has changed dramatically in the past 15 years. This has been due to the development of tyrosine kinase inhibitors (TKIs), compounds that inhib- it the activity of the oncogenic BCR-ABL protein. Imatinib (IM) was the first TKI developed for CML, and it led to high rates of complete cytogenetic responses and improved survival for patients with this disease. However, approximately one-third of patients experience IM resistance or intolerance. These patients may benefit from alternative more effective treatment options. Patients who have delayed reponses to IM are at increased risk of disease progression. As BCR-ABL activity has a critical role in disease progression by promoting genetic instability, more effective BCR-ABL inhibition may decrease the risk of disease progression. Randomized phase III studies have demonstrated that first-line treatment with dasatinib or nilotinib results in higher rates of CCyR and MMR by 12-24 months compared with IM, in addition to a lower rate of disease progression. Based on these data, it is reasonable to use second-generation TKIs in the treatment of newly diagnosed patients with CP-CML. As there are no data comparing both agents, one agent cannot be recommended over the other. Therefore, physicians should consider the BCR-ABL mutation profile and the patient’s history to make an educated decision on the best choice. The obvious debating points regarding the use of second-generation TKIs up front are: a) whether or not the benefit in early cytogenetic and molecular response will translate to a long-lasting survival benefit b) the wisdom of switching to second-generation drugs without long-term safety data and c) cost issues, especially with the prospect of generic IM in the foreseeable future.