Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial
Jane F Apperley, Jorge E Cortes, Dong-Wook Kim, Lydia Roy, Gail J Roboz, Gianantonio Rosti, Eduardo O Bullorsky, Elisabetta Abruzzese, Andreas Hochhaus, Dominik Heim, Carmino A de Souza, Richard A Larson, Jeffrey H Lipton, H Jean Khoury, Hyeoung-Joon Kim, Christian Sillaber, Timothy P Hughes, Philipp Erben, Jan Van Tornout, Richard M Stone, Jane F Apperley, Jorge E Cortes, Dong-Wook Kim, Lydia Roy, Gail J Roboz, Gianantonio Rosti, Eduardo O Bullorsky, Elisabetta Abruzzese, Andreas Hochhaus, Dominik Heim, Carmino A de Souza, Richard A Larson, Jeffrey H Lipton, H Jean Khoury, Hyeoung-Joon Kim, Christian Sillaber, Timothy P Hughes, Philipp Erben, Jan Van Tornout, Richard M Stone
Abstract
PURPOSE Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population. PATIENTS AND METHODS Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%). CONCLUSION Dasatinib is effective in patients with CML-AP after imatinib treatment failure.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Source: PubMed