Dasatinib versus imatinib (IM) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): DASISION 3-year follow-up.

Authors

null

Andreas Hochhaus

Universitätsklinikum Jena, Jena, Germany

Andreas Hochhaus , Neil P. Shah , Jorge E. Cortes , Michele Baccarani , M. Brigid Bradley-Garelik , David Dejardin , Hagop Kantarjian

Organizations

Universitätsklinikum Jena, Jena, Germany, University of California, San Francisco, San Francisco, CA, University of Texas M. D. Anderson Cancer Center, Houston, TX, University Hospital Bologna, Bologna, Italy, Bristol-Myers Squibb, Wallingford, CT, Bristol-Myers Squibb, Braine-l'Alleud, Belgium

Research Funding

Pharmaceutical/Biotech Company
Background: In the phase 3 DASISION trial of dasatinib v IM in patients (pts) with newly diagnosed CML-CP, dasatinib had higher 12-month rates of complete cytogenetic response (CCyR) and major molecular response (MMR) (Kantarjian, NEJM 2010;362:2260). By 12 months confirmed CCyR (cCCyR) rates for dasatinib v IM were 77% v 66%, P=0.001, meeting the primary endpoint. Methods: Pts were randomized to receive dasatinib 100 mg once daily (QD; n=259) or IM 400 mg QD (n=260). Results: Minimum 24-month follow-up (median 26.6 months) is reported here. 24-month molecular response rates were higher for dasatinib v IM: MMR (BCR-ABL ≤0.1%) 64% v 46%, P<0.0001; MR4 (BCR-ABL ≤0.01%) 29% v 19%, P=0.0053; MR4.5 (BCR-ABL ≤0.0032%) 17% v 8%, P=0.0032. MMR rates were higher for dasatinib in all Hasford risk groups (high 73% v 56%; intermediate 61% v 50%; low 73% v 56%). Of pts who achieved MMR at 12 months, on dasatinib v IM, 97% v 92% had maintained their MMR at 24 months, respectively. Pts receiving dasatinib v IM had faster responses; median time to CCyR and MMR was 3.2 v 6.0 and 15 v 36 months, respectively. In an intent-to-treat analysis, fewer pts receiving dasatinib (n=9; 3.5%) transformed to accelerated/blast phase v IM (n=15; 5.8%) on study or during follow-up after discontinuation. 24-month overall and progression-free survival were similar for dasatinib v IM: 95.4% v 95.2% and 93.7% v 92.1% (follow-up is ongoing). Few additional adverse events (AEs) were reported between 12 and 24 months in both arms, with grade 3/4 nonhematologic AE rates ≤1%. In each arm, 10 pts had a BCR-ABL mutation detected at time of discontinuation. For dasatinib v IM, 23% v 25% discontinued treatment for drug-related AEs (7% v 5%), progression (5% v 7%), failure (3% v 4%), unrelated AEs (2% v <1%), death (2% v <1%), and other (4% v 8%). Few pts discontinued between 12 and 24 months for dasatinib (n=19; 7%) and IM (n=16; 6%). Conclusions: Updated data with minimum 36-month follow-up will be presented, including mutation analyses in pts who discontinued, progressed, or had suboptimal response. Pts receiving dasatinib had a lower transformation rate and higher molecular responses v pts receiving IM, supporting the use of dasatinib in newly diagnosed CML-CP.

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Abstract Details

Meeting

2012 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Leukemia, Myelodysplasia, and Transplantation

Track

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Sub Track

Leukemia

Clinical Trial Registration Number

NCT00481247

Citation

J Clin Oncol 30, 2012 (suppl; abstr 6504)

DOI

10.1200/jco.2012.30.15_suppl.6504

Abstract #

6504

Abstract Disclosures

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