Leukemia & lymphoma
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Leukemia & lymphoma · Mar 2010
ReviewUse of dasatinib and nilotinib in imatinib-resistant chronic myeloid leukemia: translating preclinical findings to clinical practice.
The BCR-ABL inhibitor imatinib revolutionized the treatment of chronic myeloid leukemia (CML). However, resistance and intolerance to imatinib have emerged as substantial clinical issues. The mechanisms underlying resistance are multifactorial and may include mutations in the kinase domain of BCR-ABL, increased production of BCR-ABL, or activation of BCR-ABL-independent pathways. ⋯ Choosing the most appropriate treatment after imatinib failure may be critical in attaining the best possible long-term prognosis. The presence of certain disease characteristics (e.g. specific BCR-ABL mutations) or patient comorbidities may facilitate more effective treatment. In this review, we discuss mechanisms of imatinib resistance and preclinical and clinical data with dasatinib and nilotinib which may have potential use for guiding second-line treatment decisions.