A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA)

Abstract

Key Points In β-thalassemia major patients with severe iron burden, deferasirox was noninferior to deferoxamine for myocardial iron removal. The ejection fraction was stable during treatment for both deferasirox and deferoxamine.

Sustained improvements in myocardial T2* over 2 years in severely iron‐overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine

“…Consideration of the rate of myocardial iron removal is important, since the implications and subsequent treatment of patients with myocardial T2* values of 10 to 20 ms differ from those with values <10 ms, who are at a greater risk of heart failure. Even so, the present study demonstrated that patients could normalize their myocardial T2* to >20 ms; achieved by a greater proportion of patients at 24 months than at 12 months in both deferasirox (24.3 versus 17.6%) and DFO patients (17.2 versus 6.2%) [8]. Importantly, 72.7% of patients treated with deferasirox and 54.5% of patients treated with DFO improved from severe (T2* <10 ms) to mild-to-moderate (T2* 10-20 ms) myocardial iron overload after 24 months-a clinically important increase since the relative risk of heart failure in patients with myocardial T2* <10 ms compared with T2* >10 ms has been shown to be significantly higher (relative risk 160 [95% CI 39-653]) [20].…”

“…Detailed patient inclusion and exclusion criteria have been reported previously [8]. Briefly, patients eligible for enrollment at baseline were male or female, aged !10 years with beta thalassemia major, sideroblastic anemia, myelodysplastic dysplastic syndromes (low/intermediate-1) or Diamond-Blackfan anemia; however, only patients with beta thalassemia major fulfilled all inclusion criteria and were enrolled.…”

“…The CORDELIA study (NCT00600938) was a 1-year prospective, multinational, randomized, open-label, parallel-group, Phase II study conducted in 22 centers across 11 countries as previously reported [8]. Patients completing first year could decide to continue on deferasirox or DFO as assigned, or switch treatment upon entering a 1-year extension, if the treatment was judged by the investigator to be of therapeutic benefit.…”

“…The controlled studies evaluating the available iron chelators, deferoxamine (DFO; Desferal V R ), deferiprone (Ferriprox V R ), and deferasirox (Exjade V R ) have all demonstrated efficacy in the removal of myocardial iron with acceptable safety profiles [7][8][9][10][11][12][13]; however, many of these clinical trials were limited to 1 year. Longer-term single-arm studies with deferasirox for myocardial iron removal have shown a continuous decrease in Additional Supporting Information may be found in the online version of this article.…”

“…1 NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom; 2 Department of Haematology, University College London, London, United Kingdom; 3 Department of Paediatrics, University of Turin, Turin, Italy; 4 Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; 5 Department of Pediatric Hematology, Cairo University, Cairo, Egypt; 6 Department of Pediatrics, Ain Shams University, Cairo, Egypt; 7 Department of Pediatric Hematology-Oncology, Akdeniz University, Antalya, Turkey; 8 Department of Biochemistry, Cukurova University Medical Facility, Adana, Turkey; myocardial iron with up to 3 years of treatment with a clinically manageable safety profile [7,14,15]. CORDELIA was a large, prospective randomized study comparing deferasirox with DFO in patients with beta thalassemia major who demonstrated, at the end of 1 year, the noninferiority of deferasirox versus DFO for myocardial iron removal, with a trend for superiority (P 5 0.057) [8]. A 1-year extension to CORDELIA was planned to collect additional long-term controlled data on the efficacy and safety of deferasirox or DFO in patients with myocardial siderosis when treated for up to 2 years.…”