Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations|
|Citation:||Blood, 2009; 114(24):4944-4953|
|Publisher:||Amer Soc Hematology|
|Martin C. Müller, Jorge E. Cortes, Dong-Wook Kim, Brian J. Druker, Philipp Erben, Ricardo Pasquini, Susan Branford, Timothy P. Hughes, Jerald P. Radich, Lynn Ploughman, Jaydip Mukhopadhyay, and Andreas Hochhaus|
|Abstract:||Dasatinib is a BCR-ABL inhibitor with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Imatinib failure is commonly caused by BCR-ABL mutations. Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL mutations after prior imatinib. Among 1043 patients, 39% had a preexisting BCR-ABL mutation, including 48% of 805 patients with imatinib resistance or suboptimal response. Sixty-threedifferent BCR-ABL mutations affecting 49 amino acids were detected at baseline, with G250, M351, M244, and F359 most frequently affected. After 2 years of follow-up, dasatinib treatment of imatinib-resistant patients with or without a mutation resulted in notable response rates (complete cytogenetic response: 43% vs 47%) and durable progression-free survival (70% vs 80%). High response rates were achieved with different mutations except T315I, including highly imatinib-resistant mutations in the P-loop region. Impaired responses were observed with some mutations with a dasatinib median inhibitory concentration (IC₅₀) greater than 3nM; among patients with mutations with lower or unknown IC₅₀, efficacy was comparable with those with no mutation. Overall, dasatinib has durable efficacy in patients with or without BCR-ABL mutations.|
|Keywords:||Humans; Pyrimidines; Thiazoles; Fusion Proteins, bcr-abl; Protein Kinase Inhibitors; Treatment Outcome; DNA Mutational Analysis; Mutation; Adolescent; Adult; Aged; Aged, 80 and over; Middle Aged; Female; Male; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Randomized Controlled Trials as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Young Adult; Kaplan-Meier Estimate; Dasatinib|
|Rights:||© 2009 by The American Society of Hematology|
|Appears in Collections:||Medicine publications|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.