Combination of dasatinib with chemotherapy in previously untreated core binding factor acute myeloid leukemia: CALGB 10801

Guido Marcucci, Susan Geyer, Kristina Laumann, Weiqiang Zhao, Donna Bucci, Geoffrey L. Uy, William Blum, Ann Kathrin Eisfeld, Timothy S. Pardee, Eunice S. Wang, Wendy Stock, Jonathan E. Kolitz, Jessica Kohlschmidt, Krzysztof Mrózek, Clara D. Bloomfield, Richard M. Stone, Richard A. Larson

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Acutemyeloid leukemia (AML)witheither t(8;21)(q22;q22)or inv(16)(p13q22)/t(16;16)(p13;q22) is referred to as core binding factor (CBF) AML. Although categorized as favorable risk, long-term survival for these patients is only ∼50% to 60%. Mutated (mut) or overexpressed KIT, a gene encoding a receptor tyrosine kinase, has been found almost exclusively in CBF AML and may increase the risk of disease relapse. We tested the safety and clinical activity of dasatinib, a multi-kinase inhibitor, in combination with chemotherapy. Sixty-one adult patients with AML and CBF fusion transcripts (RUNX1/RUNX1T1 or CBFB/MYH11) were enrolled on Cancer and Leukemia Group B (CALGB) 10801. Patients received cytarabine/daunorubicin induction on days 1 to 7 and oral dasatinib 100 mg/d on days 8 to 21. Upon achieving complete remission, patients received consolidation with high-dose cytarabine followed by dasatinib 100 mg/d on days 6 to 26 for 4 courses, followed by dasatinib 100 mg/d for 12 months. Fifteen (25%) patients were older (aged ≥60 years); 67% were CBFB/MYH11-positive, and 19% harbored KITmut. There were no unexpected or dose-limiting toxicities. Fifty-five (90%) patients achieved complete remission. With a median follow-up of 45 months, only 16% have relapsed. The 3-year disease-free survival and overall survival rates were 75% and 77% (79% and 85% for younger patients [aged <60 years], and 60% and 51% for older patients). Patients with KITmut had comparable outcome to those with wild-type KIT (3-year rates: Disease-free survival, 67% vs 75%; overall survival, 73% vs 76%), thereby raising the question of whether dasatinib may overcome the negative impact of these genetic lesions.

Original languageEnglish (US)
Pages (from-to)696-705
Number of pages10
JournalBlood Advances
Volume4
Issue number4
DOIs
StatePublished - Feb 25 2020

ASJC Scopus subject areas

  • Hematology

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