Τίτλος:
Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Aydinok, Y.
Kattamis, A.
Cappellini, M.D.
El-Beshlawy, A.
Origa, R.
Elalfy, M.
Kilinç, Y.
Perrotta, S.
Karakas, Z.
Viprakasit, V.
Habr, D.
Constantinovici, N.
Shen, J.
Porter, J.B.
HYPERION Investigators
Περιοδικό:
Blood advances
Εκδότης:
American Society of Hematology
Λέξεις-κλειδιά:
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
DOI:
10.1182/blood-2014-07-586677
