LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING

Background Patients 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 methods We 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). Results We 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. Conclusions TDD-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.