A Randomized Controlled Study Evaluating the Safety and Efficacy of Deferiprone Treatment in Thalassemia Major Patients from Hong Kong

Abstract

A controlled, open-label and randomized study was conducted to evaluate the safety and efficacy of the oral iron chelator deferiprone (L1) in thalassemia major patients from Hong Kong. Forty-nine patients were recruited in total (median age: 20 years; range: 8 to 40 years). The division of the patients was determined based on liver iron content and put into either the poorly-chelated (Group I) or well-chelated (Group II) groups. In Group I, 20 patients received combined therapy of L1 daily plus desferrioxamine (DFO), in a reduced frequency of twice weekly, while the control group consisted of 16 patients who were treated with DFO alone. In Group II, six patients received L1 only, while the control group consisted of seven patients treated with DFO alone. Only patients who participated for longer than 6 months were analyzed for efficacy (n = 44). The median study period was 18 months. Transient and mild gastrointestinal upset (31%), joint pain (15%) and liver enzyme elevation (23%) were the most common side effects noted for L1. No case of neutropenia was observed in this study. Serum ferritin (SF) levels showed significant decline in the poorly-chelated patients using combined therapy (L1 and reduced frequency DFO) as compared to those on DFO alone. However, their pre- and post-study liver iron content was not significantly different. Evaluation of the well-chelated group demonstrated no significant change in SF or liver iron content in both the study and control arms. We conclude that the short-term use of L1, with or without DFO, was safe and efficacious in our Chinese patient cohort. The long-term efficacy of reducing iron overload by treatment regimens including L1 requires further study.

Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

“…The incidence of fluctuation of hepatic transaminase levels after deferiprone exposure found in our Thai patients seemed to be higher than Caucasian population [21,42,54] but somewhat similar to Chinese patients [41,59]. Around 50% of the incidences were mild and transient; patients could continue on the study drug without interruption.…”

“…These groups of patients were inadequately treated or chelation naive with very high levels of baseline serum ferritin and high iron intake from blood transfusion [11,[36][37][38][39][40][41]. Furthermore our findings that SF values were more likely to decrease in those patients who began with the highest SF values and lower iron intake from lower transfusion rate (<0.25 mg/kg/day in our study) are consistent with previous individual studies [42][43][44] and review of trends from several studies [38].…”

Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders

“…Eight studies comparing DFP to DFO were analyzed (Table 4). 5,8,[56][57][58][59][60][61] Altogether, 563 evaluable patients received DFO and 370 DFP or DFP plus DFO. The maximum observation time was nine years.…”

“…5,8 More cardiac events occurred while on DFO, and the analysis of cardiac disease free survival over the 5-year period was significantly more favorable in the DFP group. 8 LIC was measured at baseline and at the end of the trial in one study, 60 and SF in six, 8,[57][58][59][60][61] There was no significant difference in pre-and post-study LIC between patients using combined therapy and patients using DFO alone. 61 Patients receiving DFP, or DFP with DFO, showed a reduction in SF over time greater than patients who received DFO alone in two trials.…”

“…8 LIC was measured at baseline and at the end of the trial in one study, 60 and SF in six, 8,[57][58][59][60][61] There was no significant difference in pre-and post-study LIC between patients using combined therapy and patients using DFO alone. 61 Patients receiving DFP, or DFP with DFO, showed a reduction in SF over time greater than patients who received DFO alone in two trials. 57,58 Three studies were analyzed for the comparison of DFX with DFO in severely iron loaded patients 9,11,43 ( Table 4).…”