Phase II trials of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

Introduction: Chronic myeloid leukemia (CML) is a disease in which outstanding discoveries and achievements have been made over the past two decades. The use of targeted BCR-ABL protein tyrosine kinase inhibitors (TKI) has revolutionized the treatment of this disease and drastically improved its outcomes. Areas covered: Imatinib was the first TKI to be studied and results from the initial IRIS study continues to show major improvement over the historical IFN treatment. More recently, second-generation TKIs, such as dasatinib and nilotinib, and more recently bosutinib proved to be superior to imatinib: higher rates of remission and faster responses. Recently, ponatinib has shown significant efficacy against the most resistant cases of CML, including those who carry the highly resistant T315I mutations. The purpose of this article is to review the data available on different TKIs in the treatment of CML, as well as the emerging data for the treatment of resistant disease. Expert opinion: Early identification of resistant cases and enrollment in clinical trials with new drugs continue to be warranted in the appropriate setting. The use of new therapeutic strategies in an attempt to eradicate the disease will be the main focus of clinical trials in the next decade.