Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload

Blood. 2015 Jun 18;125(25):3868-77. doi: 10.1182/blood-2014-07-586677. Epub 2015 May 1.

Abstract

Deferasirox (DFX) monotherapy is effective for reducing myocardial and liver iron concentrations (LIC), although some patients may require intensive chelation for a limited duration. HYPERION, an open-label single-arm prospective phase 2 study, evaluated combination DFX-deferoxamine (DFO) in patients with severe transfusional myocardial siderosis (myocardial [m] T2* 5-<10 ms; left ventricular ejection fraction [LVEF] ≥56%) followed by optional switch to DFX monotherapy when achieving mT2* >10 ms. Mean dose was 30.5 mg/kg per day DFX and 36.3 mg/kg per day DFO on a 5-day regimen. Geometric mean mT2* ratios (Gmeanmonth12/24/Gmeanbaseline) were 1.09 and 1.30, respectively, increasing from 7.2 ms at baseline (n = 60) to 7.7 ms at 12 (n = 52) and 9.5 ms at 24 months (n = 36). Patients (17 of 60; 28.3%) achieved mT2* ≥10 ms and ≥10% increase from baseline at month 24; 15 switched to monotherapy during the study based on favorable mT2*. LIC decreased substantially from a baseline of 33.4 to 12.8 mg Fe/g dry weight at month 24 (-52%). LVEF remained stable with no new arrhythmias/cardiac failure. Five patients discontinued with mT2* <5 ms and 1 died (suspected central nervous system infection). Safety was consistent with established monotherapies. Results show clinically meaningful improvements in mT2* in about one-third of patients remaining on treatment at month 24, alongside rapid decreases in LIC in this heavily iron-overloaded, difficult-to-treat population. Combination therapy may be useful when rapid LIC reduction is required, regardless of myocardial iron overload. This trial was registered at www.clinicaltrials.gov as #NCT01254227.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Benzoates / administration & dosage*
  • Benzoates / adverse effects
  • Child
  • Deferasirox
  • Deferoxamine / administration & dosage*
  • Deferoxamine / adverse effects
  • Female
  • Heart / drug effects
  • Humans
  • Iron Chelating Agents / administration & dosage*
  • Iron Chelating Agents / adverse effects
  • Iron Overload / drug therapy*
  • Iron Overload / etiology
  • Liver / chemistry
  • Liver / drug effects
  • Male
  • Myocardium / chemistry
  • Siderophores / administration & dosage*
  • Siderophores / adverse effects
  • Transfusion Reaction
  • Triazoles / administration & dosage*
  • Triazoles / adverse effects
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01254227