## Abstract

For many patients with myelodysplastic syndromes (MDS) chronic red blood cell transfusion is the standard of care to delay or prevent disease progression and to improve function. This is not without consequence, however, as transfusion-dependent patients are at risk for developing iron overload, potentially leading to cardiac disease, diabetes and hepatic complications. Iron chelators have been widely applied to remove excess iron from the body. Once-daily deferasirox given orally achieves iron reduction with easy administration. The purpose of the study was to develop a model to compare the impact of choosing deferasirox versus no chelation in managing transfusion-dependent patients with MDS. Mortality, progression to acute myeloid leukemia (AML), and development of complications related to iron overload were central elements of this model. Simulated patients were individually subject to these risks, dependent on use of chelation. The analysis was stratified by patients’ age group (≤77, >77) and by severity of MDS (Low, Int-1, Int-2 and High) as defined by the International Prognostic Scoring System (IPSS). Event risks, utilities associated with chelation and complication status were obtained from published or presented sources and deferasirox study data. The improved rates with deferasirox versus no chelation for mortality and progression to AML were taken from recent studies by Rose et al and Leitch, respectively. Complication rates for patients receiving transfusion, and the deferasirox-related reduction in these rates, were obtained from the literature. The cost of deferasirox and management costs were estimated from data obtained from literature and other US cost data sources. All costs are reported in 2008 US$. Utility values associated with deferasirox and no chelation were calculated as 0.74 and 0.67 using SF-36 measures from a substudy of a 1-year, open-label, single-arm, multi-center trial evaluating the efficacy and safety of oral chelation therapy. Costs and benefits were discounted at 3% per year. Univariate sensitivity analyses were implemented. Initial 10-year results estimated a cost per patient of$217,785 with deferasirox and $120,505 with no chelation. Deferasirox management resulted in 4.94 years survival (discounted) and 3.18 QALYs per patient. Compared with no chelation, deferasirox yielded an additional 1.63 years survival and 1.42 QALY. Resultant cost-effectiveness ratio was$68,699/QALY gained. Results of sensitivity analyses and other scenarios predicted a cost/QALY as low as \$44,068. Chelation therapy with deferasirox is predicted to result in improved survival and substantially fewer complications due to excess iron accumulation in the range of accepted cost/QALY.

Disclosures: Bozkaya:Novartis: Research Funding. Migliaccio-Walle:Novartis: Research Funding. Baladi:Novartis: Employment.

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