BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase Journal Article


Authors: Hughes, T. P.; Saglio, G.; Quintás-Cardama, A.; Mauro, M. J.; Kim, D. W.; Lipton, J. H.; Bradley-Garelik, M. B.; Ukropec, J.; Hochhaus, A.
Article 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. © 2015 Macmillan Publishers Limited All rights reserved.
Keywords: controlled study; treatment response; gene mutation; major clinical study; disease course; treatment duration; comparative study; follow up; imatinib; randomized controlled trial; clinical assessment; cancer screening; cytogenetics; dasatinib; chronic myeloid leukemia; mutational analysis; cancer therapy; drug dose escalation; chronic disease; allogeneic hematopoietic stem cell transplantation; phase 3 clinical trial; bcr abl protein; nilotinib; drug substitution; drug treatment failure; treatment withdrawal; chronic patient; human; priority journal; article; chronic myeloid leukemia in chronic phase
Journal Title: Leukemia
Volume: 29
Issue: 9
ISSN: 0887-6924
Publisher: Nature Publishing Group  
Date Published: 2015-09-01
Start Page: 1832
End Page: 1838
Language: English
DOI: 10.1038/leu.2015.168
PROVIDER: scopus
PMCID: PMC4559757
PUBMED: 26118315
DOI/URL:
Notes: Export Date: 2 October 2015 -- Source: Scopus
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  1. Michael John Mauro
    267 Mauro