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

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.

• Authors: Yesim Aydinok, Antonis Kattamis, M Domenica Cappellini, Amal El-Beshlawy, Raffaella Origa, Mohsen Elalfy, Yurdanur Kilinç, Silverio Perrotta, Zeynep Karakas, Vip Viprakasit, Dany Habr, Niculae Constantinovici, Junwu Shen, John B Porter, HYPERION Investigators
• Journal: Blood (Blood) Vol. 125 Issue 25 Pg. 3868-77 (Jun 18 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 25934475 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society of Hematology.

Chemical References

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

Topics

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