Loss of response to imatinib: mechanisms and management.

摘要: The treatment of chronic myeloid leukemia (CML) has been revolutionized by the small molecule BCR-ABLselective kinase inhibitor imatinib. Although imatinib is highly effective initially and generally well-tolerated, relapse increasingly encountered clinically. Until recently, for majority CML patients with disease no longer responsive to imatinib, as well intolerance, few therapeutic options existed. Our understanding major mechanisms resistance led clinical development two novel BCR-ABL inhibitors that harbor significant promise in early trial experience. These agents, dasatinib (BMS-354825) AMN107, are more potent than moreover, activity against nearly all imatinib-resistant domain mutant forms tested vitro. Notably, neither these compounds BCR-ABL/T315I mutation. potential availability medications intolerant cases expected further complicate timing other therapies, such allogeneic stem cell transplantation. Additionally, periodic genotyping screen drug-resistant mutations may play an important role future management cases. phase have durable hematologic cytogenetic responses a subset loses their best response despite continued treatment. Some progress accelerated or blast CML, while patients, consists loss previously established response. A minority does not achieve response, likely phase. 1