By Jill Stein
VIENNA, AUSTRIA -- June 11, 2007 -- With appropriate dosing, deferasirox effectively controls iron levels in a population of patients with beta-thalassaemia who are heavily transfused and unable to achieve successful iron chelation with deferoxamine and/or deferiprone, according to data reported here at the 12th Congress of the European Haematology Association (EHA).
Ali Taher, MD, associate professor, department of haematology-oncology, American University of Beirut, Beirut, Lebanon, and associates examined the efficacy and safety of deferasirox in 252 beta-thalassaemia patients with a high iron burden and history of inadequate chelation.
Deferasirox is a once-daily, oral iron chelator.
All participants had been unsuccessfully treated with prior monotherapy or combination chelation therapy with deferoxamine and/or deferiprone, due to unacceptable toxicity or poor response to deferoxamine and/or deferiprone, or documented noncompliance with deferoxamine.
All patients had baseline liver iron concentrations (LIC) at or greater than 2 mg/g dw, serum ferritin (SF) levels 500 ng/mL or greater, and initially received deferasirox at a dose of 20 mg/kg/day. Based on results from another study, the protocol was amended midstudy to allow dose adjustment according to monthly serum ferritin trends. LIC was measured at baseline and at the end of the study.
Treatment success, the primary endpoint, was defined as LIC reductions of 3 mg/g dw or greater if the baseline level was 10 mg/g dw or greater, or a final LIC of 1 to 7 mg/g dw if the baseline level was 2 to <7 mg/g dw or >/=7 to <10.
Overall mean reduction in LIC from baseline was 3.5 mg Fe/g dw. In all patients with baseline LIC >7 mg Fe/g dw, whose therapeutic goal was LIC reduction, the decrease was 4.0 mg Fe/g dw, P <.001). In those with baseline LIC </=7 mg Fe/g dw, whose therapeutic goal was LIC maintenance, the change was 0.9 mg Fe/g dw.
Overall success rate according to prospectively defined criteria was 56.3% (P =.02), Dr. Taher said in a presentation on June 9th.
Median serum ferritin levels seemed to decrease in the adult population during the study but were relatively unchanged in the paediatric population.
At the end of the study, there was a reduction from baseline in the median serum ferritin level of 230 ng/nL.
Dose escalation to 25 or 30 mg/kg daily was required in 76.2% of patients because they had not achieved their target reduction in iron burden as measured by serum ferritin.
Results also showed that 98% patients completed 1 year of treatment.
Deferasirox had an adverse effect profile that was clinically manageable with regular patient monitoring, according to the researchers. The adverse events in this 1-year study were consistent with prior observations in studies of patients with beta-thalassaemia.
Dr. Taher said that the effect of higher doses on iron burden is being further examined in an ongoing extension trial.
The study was sponsored by Novartis.
[Presentation title: Treatment With the Once-Daily, Oral Iron Chelator Deferasirox (Exjade, ICL670) is Effective and Well Tolerated in Beta-Thalassaemia Patients With High Iron Burden. Abstract 808]
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