TY - JOUR
TI - Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload
AU - Aydinok, Y.
AU - Kattamis, A.
AU - Cappellini, M.D.
AU - El-Beshlawy, A.
AU - Origa, R.
AU - Elalfy, M.
AU - Kilinç, Y.
AU - Perrotta, S.
AU - Karakas, Z.
AU - Viprakasit, V.
AU - Habr, D.
AU - Constantinovici, N.
AU - Shen, J.
AU - Porter, J.B.
AU - HYPERION Investigators
JO - Blood advances
PY - 2015
VL - 125
TODO - 25
SP - 3868-3877
PB - American Society of Hematology
SN - null
TODO - 10.1182/blood-2014-07-586677
TODO - creatinine;  deferasirox;  deferoxamine;  ferritin;  iron;  benzoic acid derivative;  deferasirox;  deferoxamine;  iron chelating agent;  siderophore;  triazole derivative, abdominal pain;  adult;  arthritis;  Article;  central nervous system infection;  child;  creatinine blood level;  diarrhea;  disease control;  disease severity;  DRESS syndrome;  drug effect;  drug safety;  drug withdrawal;  female;  ferritin blood level;  fever;  geometry;  heart arrhythmia;  heart function;  heart hemosiderosis;  heart left ventricle ejection fraction;  human;  iron overload;  liver hemosiderosis;  major clinical study;  male;  minimum inhibitory concentration;  monotherapy;  multicenter study;  nausea;  open study;  phase 2 clinical trial;  priority journal;  prospective study;  pruritus;  teratoma;  adolescent;  adverse effects;  blood transfusion;  chemistry;  clinical trial;  drug effects;  heart;  heart muscle;  iron overload;  liver;  young adult, Adolescent;  Adult;  Benzoates;  Blood Transfusion;  Child;  Deferoxamine;  Female;  Heart;  Humans;  Iron Chelating Agents;  Iron Overload;  Liver;  Male;  Myocardium;  Siderophores;  Triazoles;  Young Adult
TODO - 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. © 2015 by The American Society of Hematology.
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