Patients with transfusion dependent thalassemia can experience iron overload and this can lead to organ damage, especially cardiomyopathy and liver cirrhosis. Deferasirox once daily is given at a dose of 30 mg/kg/day but about 30% of patients cannot maintain a negative iron balance. Such patients require doses greater than 30 mg/kg/day. The dose of deferasirox can be increased to 40 mg/kg/day with an acceptable safety profile.
Studies have shown that twice-daily deferasirox improved the clinical efficacy of transfusion-dependent thalassemia patients who did not respond to once-daily deferasirox. However, the effectiveness, safety, and long-term tolerability are unknown in these patients. Therefore, a retrospective study was conducted to determine the long-term efficacy and safety of twice-daily deferasirox in transfusion-dependent thalassemia patients who did not respond to once-daily deferasirox.
In this study, patients who did not respond to deferasirox once daily were switched to deferasirox twice daily, at the same dose as before. The results of this study are: (n= 22); The median age of the patients was 9.2 years. The median blood transfusion was 216 mL/kg/year. The median period of therapy with deferasirox twice daily was 30 months. The median dose of deferasirox once daily was 37.5 mg/kg/day. A total of 18 patients responded with deferasirox twice daily (81.8%). Median serum ferritin levels decreased at 12 months (2486 ng/mL to 1456 ng/mL [p= 0.006]) and 24 months (2486 ng/mL to 881.5 ng/mL [p= 0.005]). Median liver iron levels decreased at 12 months (6.6 mg/g dry weight to 3.5 mg/g dry weight [p= 0.006]) and 24 months (6.6 mg/g dry weight to 2.7 mg). /g dry weight [p= 0.005]).
No gastrointestinal intolerance or skin reactions, severe transaminitis, and abnormal renal function tests have been reported. A total of 3 patients had grade 1 proteinuria that improved without interruption of therapy or dose reduction. Creatinine increases but is still within the normal range for age. Ophthalmic and audiometric examinations were normal during therapy. A total of 11 patients who responded to deferasirox twice daily experienced a dose reduction.
The conclusion of this study is that deferasirox twice a day is effective in reducing ferritin and liver iron levels in transfusion dependent thalassemia patients who do not respond to deferasirox once daily and can be tolerated by the patient.
Image: Illustration (source:by katemangostar - www.freepik.com)
Reference:
1. Buaboonnam J, Takpradit C, Viprakasit V, Narkbunnam N, Vathana N, Phuakpet K, et al. Long-term effectiveness, safety, and tolerability of twice-daily dosing with deferasirox in children with transfusion-dependent thalassemias unresponsive to standard once-daily dosing. Mediterr J Hematol Infect Dis. 2021;13(1):e2021065.
2. Pongtanakul B, Viprakasit V. Twice daily dosing of deferasirox significantly improves clinical efficacy in transfusion dependent thalassemias who were inadequate responders to standard once daily dose. Blood 2012;120(21):1026.
