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.
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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)
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Copyright | © 2015 by The American Society of Hematology. |
Chemical References |
- Benzoates
- Iron Chelating Agents
- Siderophores
- Triazoles
- Deferoxamine
- Deferasirox
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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
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