Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase: long-term efficacy and endocrine analysis.
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Chronic myeloid leukemia (CML) accounts for 2-3% of childhood leukemias. CA180 226 is a prospective phase 2 trial evaluating dasatinib in pediatric patients with newly diagnosed (ND) or imatinib resistant/intolerant (IM R/I) chronic phase CML (CML CP). Analyses showed rapid molecular responses, but long term efficacy, deep molecular responses (DMR), and endocrine effects of tyrosine kinase inhibitors (TKIs) in children have not been reported. This study reports long term outcomes in the largest pediatric cohort to date with endocrine assessment during TKI therapy. ND patients received dasatinib tablets (Cohort 3A) or oral suspension (Cohort 3B), while IM R/I patients were enrolled in Cohort 1. Cohorts 3A and 1 received 60 mg/m² daily; Cohort 3B received 72 mg/m² daily. Median follow-up was 94.8 months for Cohort 3 and 92.4 months for Cohort 1. Height z scores declined over the first few years of therapy particularly in prepubertal children, whereas BMI and bone density changes were mild. Thyroid and gonadal abnormalities were infrequent. Major molecular responses (MMR) occurred within the first 2 years, with 96 month MMR rates of 83.3% in Cohort 3 and 69.0% in Cohort 1. DMR accumulated, with MR4 and MR4.5 rates of 54.8% and 41.7% in Cohort 3 and 37.9% and 27.6% in Cohort 1 at 96 months, respectively. Median progression free and disease free survival were not reached. These long-term data demonstrate durable dasatinib efficacy to induce DMR alongside initial height z-score decline and modest additional endocrine effects, providing important insight into TKI therapy in pediatric CML-CP. NCT00777036.