title: Dasatinib-associated major molecular responses in patients with chronic myeloid leukemia in chronic phase following imatinib failure: response dynamics and predictive value.
abstract: Dasatinib is a highly potent BCR-ABL inhibitor that has shown durable efficacy in patients with chronic phase (CP) chronic myeloid leukemia (CML) after resistance, suboptimal response, or intolerance to prior imatinib. In patients with CML, BCR-ABL transcript measurement is the most sensitive method for assessing minimal residual disease. Here, molecular responses were analyzed in 1067 patients with CML-CP treated with dasatinib during phase II/III trials. After 3, 6, 12, and 24 months of follow-up, a major molecular response (MMR) was achieved by 12, 22, 35, and 40% of patients, respectively. The 24-month MMR rate was 34% in patients with resistance or suboptimal response to imatinib (n=829) and 63% in imatinib-intolerant patients (n=238). Among patients who had achieved a complete cytogenetic response (CCyR), 72% also achieved MMR. Responses with dasatinib 100 mg once daily were similar to other doses. In landmark analyses, 24-month progression-free survival was higher in patients who had achieved MMR or CCyR at 12 months than in those without MMR or CCyR at 12 months. MMR at 12 months was associated with a longer duration of CCyR. Overall, this analysis shows that dasatinib treatment results in high MMR rates in patients with CML-CP after imatinib failure.
authors.affiliation: III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany. andreas.hochhaus@med.uni-jena.de
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.forename: M C
authors.initials: MC
authors.lastname: Müller
authors.forename: J
authors.initials: J
authors.lastname: Radich
authors.forename: S
authors.initials: S
authors.lastname: Branford
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: B
authors.initials: B
authors.lastname: Hanfstein
authors.forename: P
authors.initials: P
authors.lastname: Rousselot
authors.forename: D-W
authors.initials: DW
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Lipton
authors.forename: E
authors.initials: E
authors.lastname: Bleickardt
authors.forename: A
authors.initials: A
authors.lastname: Lambert
authors.forename: T P
authors.initials: TP
authors.lastname: Hughes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D053843:DNA Mismatch Repair; D000069439:Dasatinib; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib