Abstract |
Treatment of advanced-phase chronic myeloid leukemia (CML) remains unsatisfactory. Single-agent tyrosine kinase inhibitors have modest and short-lived activity in this setting. We conducted a phase I/II study to determine safety and efficacy of the combination of dasatinib and decitabine in patients with advanced CML. Two different dose schedules were investigated with a starting decitabine dose of either 10 mg/m2 or 20 mg/m2 daily for 10 days plus dasatinib 100 mg daily. The target dose level was decitabine 10 mg/m2 or 20 mg/m2 daily for 10 days plus dasatinib 140 mg daily. Thirty patients were enrolled, including seven with accelerated-phase CML, 19 with blast-phase CML, and four with Philadelphia-chromosome positive acute myeloid leukemia. No dose-limiting toxicity was observed at the starting dose level with either schedule. Grade ≥3 treatment emergent hematological adverse events were reported in 28 patients. Thirteen patients (48%) achieved a major hematologic response and six (22%) achieved a minor hematologic response, with 44% of these patients achieving a major cytogenetic response and 33% achieving a major molecular response. Median overall survival (OS) was 13.8 months, with significantly higher OS among patients who achieved a hematologic response compared to non-responders (not reached vs 4.65 months; P < .001). Decitabine plus dasatinib is a safe and active regimen in advanced CML. Further studies using this combination are warranted.
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Authors | Yasmin Abaza, Hagop Kantarjian, Yasmin Alwash, Gautam Borthakur, Richard Champlin, Tapan Kadia, Guillermo Garcia-Manero, Naval Daver, Farhad Ravandi, Srdan Verstovsek, Jan Burger, Zeev Estrov, Maro Ohanian, Miranda Lim, Naveen Pemmaraju, Elias Jabbour, Jorge Cortes |
Journal | American journal of hematology
(Am J Hematol)
Vol. 95
Issue 11
Pg. 1288-1295
(11 2020)
ISSN: 1096-8652 [Electronic] United States |
PMID | 32681739
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2020 Wiley Periodicals LLC. |
Chemical References |
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, adverse effects)
- Blast Crisis
(blood, drug therapy, mortality)
- Dasatinib
(administration & dosage, adverse effects)
- Decitabine
(administration & dosage, adverse effects)
- Disease-Free Survival
- Female
- Humans
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
(blood, drug therapy, mortality)
- Leukemia, Myeloid, Acute
(blood, drug therapy, mortality)
- Male
- Middle Aged
- Survival Rate
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