Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload.
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.
Department of Pediatric Hematology, Ege University Hospital, Izmir, Turkey;
Yesim
Y
Aydinok
First Department of Pediatrics, University of Athens, Athens, Greece;
Antonis
A
Kattamis
Universitá di Milano, Ca Granda Foundation Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy;
M Domenica
MD
Cappellini
Department of Hematology, Pediatric Hospital, Cairo University, Cairo, Egypt;
Amal
A
El-Beshlawy
Ospedale Regionale per le Microcitemie, University of Cagliari, Cagliari, Italy;
Raffaella
R
Origa
Thalassemia Center, Children's Hospital, Ain Shams University, Cairo, Egypt;
Mohsen
M
Elalfy
Medical Facility, Cukurova University, Adana, Turkey;
Yurdanur
Y
Kilinç
Department of Woman, Child and of General and Specialist Surgery, I°Policlinico II°Università di Napoli, Naples, Italy;
Silverio
S
Perrotta
Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey;
Zeynep
Z
Karakas
Department of Pediatrics and Thalassemia Center, Siriraj Hospital, Mahidol University, Bangkok, Thailand;
Vip
V
Viprakasit
Novartis Pharmaceuticals, East Hanover, NJ;
Dany
D
Habr
Novartis Pharma AG, Basel, Switzerland; and.
Niculae
N
Constantinovici
Novartis Pharmaceuticals, East Hanover, NJ;
Junwu
J
Shen
Department of Hematology, UCL Cancer Institute, University College London, London, United Kingdom.
John B
JB
Porter
D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D000077588:Deferasirox; D003676:Deferoxamine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000737:chemistry; D017262:Siderophores / Q000008:administration & dosage* / Q000009:adverse effects; D065227:Transfusion Reaction; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
D001565:Benzoates; D007502:Iron Chelating Agents; D017262:Siderophores; D014230:Triazoles; D003676:Deferoxamine; D000077588:Deferasirox