Effect of Dasatinib Vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized, Open-Label, Multicenter Study of the Chinese Children's Cancer Group

OBJECTIVE To determine whether dasatinib given at 80 mg/m² is more effective than imatinib at 300 mg/m² to improve event-free survival of children with Philadelphia chromosome-positive ALL, in the context of intensive chemotherapy without prophylactic cranial irradiation.

DESIGN, SETTING, AND PARTICIPANTS This open-label phase III randomized study was conducted at 20 hospitals in China. Enrollment began in January 2015 and randomization was stopped in October 2018 when the early stopping criterion of the trial was met. Patients aged between 0 and 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined and 1 died before treatment.

INTERVENTIONS Patients were randomized to receive daily dasatinib (n=92) or imatinib (n=97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy.

MAIN OUTCOMES AND MEASURES The primary outcome was event-free survival, analyzed by intent-to-treat. The secondary outcomes were relapse, toxic death, and overall survival.

RESULTS With a median follow-up of 26.1 months (IQR 16.3-34.1), the 4-year event-free survival rate was 71.0% (95% CI 56.2-89.6) in the dasatinib group and 48.9% (95% CI 32.0-74.5, p=0.005) in the imatinib group (hazard ratio 2.36, 95% CI 1.27-4.40, p=0.007). The 4-year cumulative risk of any relapse was 19.8% (95% CI 4.2-35.4) in the dasatinib group and 34.4% (95% CI 15.6-53.2) in the imatinib group (p=0.01), while the 4-year cumulative risk of an isolated central-nervous-system relapse was 2.7% (95% CI 0.0-8.1) in the dasatinib group and 8.4% (95% CI -1.2-15.6) in the imatinib group (p=0.06). There were no significant differences in the frequency of severe toxicities between the two treatment groups.

CONCLUSION AND RELEVANCE Intensive chemotherapy including dasatinib at 80 mg/m² per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared to imatinib at 300 mg/m² per day and provided excellent control of central-nervous-system leukemia without the use of prophylactic cranial irradiation.