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.
Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload / Y. Aydinok, A. Kattamis, M.D. Cappellini, A. El-Beshlawy, R. Origa, M. Elalfy, Y. Kilinç, S. Perrotta, Z. Karakas, V. Viprakasit, D. Habr, N. Constantinovici, J. Shen, J.B. Porter. - In: BLOOD. - ISSN 0006-4971. - 125:25(2015 Jun 18), pp. 3868-3877. [10.1182/blood-2014-07-586677]
Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload
M.D. Cappellini;
2015
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.File | Dimensione | Formato | |
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