TY - JOUR
T1 - Combination of dasatinib with chemotherapy in previously untreated core binding factor acute myeloid leukemia
T2 - CALGB 10801
AU - Marcucci, Guido
AU - Geyer, Susan
AU - Laumann, Kristina
AU - Zhao, Weiqiang
AU - Bucci, Donna
AU - Uy, Geoffrey L.
AU - Blum, William
AU - Eisfeld, Ann Kathrin
AU - Pardee, Timothy S.
AU - Wang, Eunice S.
AU - Stock, Wendy
AU - Kolitz, Jonathan E.
AU - Kohlschmidt, Jessica
AU - Mrózek, Krzysztof
AU - Bloomfield, Clara D.
AU - Stone, Richard M.
AU - Larson, Richard A.
N1 - Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/2/25
Y1 - 2020/2/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85082201180&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2019000492
DO - 10.1182/bloodadvances.2019000492
M3 - Article
C2 - 32092139
AN - SCOPUS:85082201180
SN - 2473-9529
VL - 4
SP - 696
EP - 705
JO - Blood Advances
JF - Blood Advances
IS - 4
ER -