title: BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase.
abstract: BCR-ABL1 mutations are a common, well-characterized mechanism of resistance to imatinib as first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). Less is known about mutation development during first-line treatment with dasatinib and nilotinib, despite increased use because of higher response rates compared with imatinib. Retrospective analyses were conducted to characterize mutation development in patients with newly diagnosed CML-CP treated with dasatinib (n=259) or imatinib (n=260) in DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML-CP), with 3-year minimum follow-up. Mutation screening, including patients who discontinued treatment and patients who had a clinically relevant on-treatment event (no confirmed complete cytogenetic response (cCCyR) and no major molecular response (MMR) within 12 months; fivefold increase in BCR-ABL1 with loss of MMR; loss of CCyR), yielded a small number of patients with mutations (dasatinib, n=17; imatinib, n=18). Dasatinib patients had a narrower spectrum of mutations (4 vs 12 sites for dasatinib vs imatinib), fewer phosphate-binding loop mutations (1 vs 9 mutations), fewer multiple mutations (1 vs 6 patients) and greater occurrence of T315I (11 vs 0 patients). This trial was registered at www.clinicaltrials.gov as NCT00481247.
authors.affiliation: Cancer Theme, SAHMRI, Division of Haematology, SA Pathology, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: T P
authors.initials: TP
authors.lastname: Hughes
authors.affiliation: University of Turin, Orbassano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Saglio
authors.affiliation: MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Quintás-Cardama
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mauro
authors.affiliation: Department of Hematology and Cancer Research Institute, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
authors.forename: D-W
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: J H
authors.initials: JH
authors.lastname: Lipton
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Bradley-Garelik
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ukropec
authors.affiliation: Department of Hematology/Oncology, Universitätsklinikum Jena, Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
mesh_terms: D004252:DNA Mutational Analysis; D000069439:Dasatinib / Q000494:pharmacology / Q000627:therapeutic use*; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology / Q000627:therapeutic use*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D009154:Mutation / Q000187:drug effects; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib