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

Am J Hematol. 2015 Feb;90(2):91-6. doi: 10.1002/ajh.23876. Epub 2014 Nov 19.

Abstract

Long-term controlled studies are needed to inform on the clinical benefit of chelation therapy for myocardial iron removal in transfusion-dependent beta thalassemia patients. In a 1-year nonrandomized extension to the CORDELIA study, data collected from patients with myocardial siderosis provided additional information on deferasirox or deferoxamine (DFO) efficacy and safety. Myocardial (m)T2* increased from baseline 11.6 to 15.9 ms in patients receiving deferasirox for 24 months (n = 74; geometric mean [Gmean ] ratio of month 24/baseline 1.38 [95% confidence interval 1.28, 1.49]) and from 10.8 to 14.2 ms in those receiving DFO (n = 29; Gmean ratio 1.33 [1.13, 1.55]; P = 0.93 between groups). Improved mT2* with deferasirox was evident across all subgroups evaluated irrespective of baseline myocardial (mT2* < 10 vs. ≥ 10 ms) or liver (LIC <15 vs. ≥15 mg Fe/g dw) iron burden. Mean LVEF was stable and remained within normal limits with deferasirox or DFO. Liver iron concentration decreased from high baseline values of 30.6 ± 18.0 to 14.4 ± 16.6 mg Fe/g dw at month 24 in deferasirox patients and from 36.8 ± 15.6 to 11.0 ± 12.1 mg Fe/g dw in DFO patients. The long-term safety profile of deferasirox or DFO was consistent with previous reports; serious drug-related AEs were reported in 6.8% of deferasirox and 6.9% of DFO patients. Continued treatment of severely iron-overloaded beta thalassemia patients with deferasirox or DFO led to sustained improvements in myocardial iron irrespective of high or low baseline myocardial or liver iron burden, in parallel with substantial improvements in liver iron (Clinicaltrials.gov identifier: NCT00600938).

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Benzoates / adverse effects
  • Benzoates / therapeutic use*
  • Chelation Therapy
  • Child
  • Deferasirox
  • Deferoxamine / adverse effects
  • Deferoxamine / therapeutic use*
  • Female
  • Humans
  • Iron / metabolism*
  • Iron Chelating Agents / adverse effects
  • Iron Chelating Agents / therapeutic use*
  • Iron Overload / drug therapy*
  • Iron Overload / etiology
  • Iron Overload / metabolism
  • Iron Overload / pathology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Prospective Studies
  • Transfusion Reaction
  • Treatment Outcome
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*
  • beta-Thalassemia / metabolism
  • beta-Thalassemia / pathology
  • beta-Thalassemia / therapy

Substances

  • Benzoates
  • Iron Chelating Agents
  • Triazoles
  • Iron
  • Deferoxamine
  • Deferasirox

Associated data

  • ClinicalTrials.gov/NCT00600938