Long-Term Effectiveness, Safety, and Tolerability of Twice-Daily Dosing with Deferasirox in Children with Transfusion-Dependent Thalassemias Unresponsive to Standard Once-Daily Dosing.

Abstract

BackgroundPatients with transfusion-dependent thalassemia (TDT) risk iron overload and require iron chelation therapy. Second-line therapy is warranted for patients demonstrating poor chelation responses.Patients and methodsWe retrospectively studied the serum-ferritin (SF), and liver-iron-concentration (LIC) outcomes of patients with TDT treated with twice-daily dosing of deferasirox (TDD-DFX) > 24 months, after failing to respond to once-daily deferasirox (OD-DFX).ResultsWe enrolled 22 OD-DFX nonresponders (14 males and eight females; median age, 9.2 [3–15.5] years). The median blood transfusion was 216 (206–277) ml/kg/year. The median TDD-DFX treatment period was 30 (24–35) months. Before initiating TDD-DFX, the median SF level was 2,486 (1,562–8,183) ng/ml, while the median LIC was 6.6 (3.2–19) mg/g dry wt. There were 18 TDD-DFX responders (81.8%) and 4 TDD-DFX nonresponders. The median SF-level change was −724 (−4,916 to 1,490) ng/mL. The median LIC change was −2.14 (−13.7 to 6.8) mg/g dry wt. The 1-year and 2-year SF levels and LICs were statistically significant (SF, P = 0.006/0.005; and LIC, 0.006/0.005, respectively). There were no treatment interruptions secondary to adverse events. In the follow-up of the TDD-DFX responder group, 11 of the 18 had a reduced dose, whereas the remaining seven continued with the same dose.ConclusionsTDD-DFX appears to be an alternative treatment approach for patients refractory to OD-DFX, with a favorable long-term safety profile. Further studies with larger groups and pharmacogenetic analyses of OD-DFX responders are warranted to determine the efficacy and safety profile of TDD-DFX.