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

• Published in: Leukemia Vol. 29; no. 9; pp. 1832 - 1838
• Main 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-09-2015; Nature Publishing Group
• Subjects: 38/23; 38/77; 38/90; 631/67; 692/699; 692/699/67/1059/99; 692/699/67/1990/283/1896; 692/699/67/68; 692/700/565/1436/434; Cancer Research; Care and treatment; Chronic myeloid leukemia; Comparative analysis; Critical Care Medicine; Dasatinib; Dasatinib - pharmacology; Dasatinib - therapeutic use; DNA Mutational Analysis; Dosage and administration; Drug therapy; Follow-Up Studies; Fusion Proteins, bcr-abl - genetics; Gene mutations; Genetic aspects; Health aspects; Hematology; Humans; Identification and classification; Imatinib Mesylate - pharmacology; Imatinib Mesylate - therapeutic use; Intensive; Internal Medicine; Leukemia, Myeloid, Chronic-Phase - drug therapy; Leukemia, Myeloid, Chronic-Phase - genetics; Leukemia, Myeloid, Chronic-Phase - mortality; Medicine; Medicine & Public Health; Mutation - drug effects; Oncology; Original; original-article; Prognosis; Time Factors; Treatment Outcome
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2015.168

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.