Accelerated-Phase CML: Is Dasatinib Plus Decitabine Active?
Posted: Friday, October 2, 2020
A recent article published in the American Journal of Hematology presented findings from a phase I/II study examining the efficacy and safety of combining the tyrosine kinase inhibitor dasatinib with the hypomethylating agent decitabine in treating patients with accelerated-phase chronic myeloid leukemia (CML). Jorge Cortes, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues, stated that traditional single-arm tyrosine kinase treatments often yielded short-lived, modest responses, especially in patients with advanced-phase CML.
A total of 30 patients were enrolled in the study, including patients with accelerated-phase CML (7), blast-phase CML (19), and Philadelphia chromosome–positive acute myeloid leukemia (4). Two different dose schedules were investigated, with the target dose set at 10 mg/m2 or 20 mg/m2 of decitabine daily for 10 days plus 140 mg of dasatinib daily.
A total of 13 patients achieved a major hematologic response, and 6 achieved a minor hematologic response. The median overall survival was 13.8 months, with significantly higher overall survival among patients who achieved a hematologic response compared with those who did not (not reached vs. 4.65 months; P < .001). Safety analyses revealed that 28 patients had adverse events greater than or equal to 3, but no dose-limiting toxicities at the starting doses of the schedules tested. Efficacy analyses with the novel combination therapy revealed that nearly half of treated patients achieved a major hematologic event, and there was no dose-limiting toxicity at the starting dose with either dosing schedule used.
Dr. Cortes and colleagues concluded: “Decitabine plus dasatinib is a safe and novel approach for managing patients with advanced CML, with a survival probability among responders that appears better than what would be expected with either agent alone.”
Disclosure: For full disclosure of the study authors, visit wiley.com.