Program Overview
Chronic myelogenous leukemia (CML) accounts for 15% of all adult leukemias. CML is characterized by the detection of the Bcr-Abl translocation, a reciprocal translocation between chromosomes 9 and 22 that results in the constitutive activation of its Abl tyrosine kinase component. In turn, the activated Bcr-Abl kinase induces a vast array of downstream signaling pathways that ultimately leads to cellular transformation. With the advent of tyrosine kinase inhibitor (TKI) therapy, rationally designed drugs have become integral to the treatment of patients with CML. Imatinib has been the standard first-line treatment for CML, as it inhibits the aberrant kinase signaling activity of the Bcr-Abl fusion protein. Since the introduction of imatinib, patient outcomes have improved radically. However, an increasing number of patients with advanced disease have acquired resistance to or become intolerant to imatinib. Furthermore, upregulation of other kinases and downstream effectors have been linked to the leukemogenesis of CML. The clinical application of new TKIs such as dasatinib and nilotinib shows promise in treating patients with CML, particularly in those patients intolerant or resistant to imatinib. Therefore, newly approved and investigational treatments have the potential to overcome the issue of imatinib intolerance or resistance and to further improve patient outcomes.
This CME-certified dinner meeting series specifically reviews current approaches for the management of CML and addresses new lines of targeted molecular therapy for patients who are imatinib-intolerant and -resistant. Mechanisms by which patients become resistant to imatinib are explored, such as altered Bcr-Abl activity resulting from mutation. The program also explains the basis of second-generation TKIs as more potent and more selective targeted molecular therapies for CML treatment. Finally, the trials evaluating the clinical impact of dasatinib, nilotinib, and several investigational TKIs, which exhibit activity in many patients who are intolerant or have become resistant to imatinib, are discussed.
