Abstract

Introduction: Approximately 60% of patients with myelodysplastic syndromes (MDS) require ongoing red blood cell transfusions, which can lead to significant iron overload and associated morbidities. Historically, many of these patients have not received iron chelation therapy due to burdensome administration of deferoxamine. Deferasirox (Exjade®, ICL670) is a once-daily, oral iron chelator recently approved for the treatment of chronic iron overload due to blood transfusions. This ongoing study is designed to evaluate the efficacy and safety of deferasirox in Low/Int-1-risk MDS patients. In addition, this is the first prospective, multicenter trial to evaluate liver iron concentration (LIC) using the MRI R2 parameter in this population.

Methods: This ongoing study will enroll 30 patients at three US centers. Deferasirox will be administered at 20–30 mg/kg/day for 12 months. Iron burden is being monitored by monthly serum ferritin evaluations, and LIC by MRI R2 at baseline, 6 and 12 months. Serum iron, transferrin, transferrin saturation, labile plasma iron (LPI), and urinary hepcidin are being assessed throughout the study. In addition, serum creatinine, calculated creatinine clearance, echocardiograms and hematological status are being monitored. In this report, we are presenting the baseline data for the currently enrolled patients.

Results: As of May 2006, 14 patients (9 male, 5 female; aged 55–81 years) were enrolled. All patients were Caucasian with equal distribution of Low- and Int-1-risk MDS. The mean interval from MDS diagnosis to screening was 4 years, ranging from <1 to 12 years. The table summarizes baseline iron parameters in these patients:

ParameternMean ± SDMedianRangeNormal range
n/a, not applicable 
LIC, mg Fe/g dw 14 21.8 ± 11.0 23.5 3.8–40.5 <1.3 
Serum ferritin,μg/L 14 4645 ± 3804 3534.5 1433–15380 20–360 
Serum iron, μg/dL 14 205.9 ± 26.5 200 165.9–252.0 50–160 
Transferrin, mg/dL 14 143 ± 19 142.5 106–172 200–400 
Transferrin saturation, % 14 113.8 ± 8.5 114 95–124 15–50 
LPI, μmol/L 14 0.7 ± 0.7 0.6 0–1.9 
Num. of lifetime transfusions 14 106.3 ± 115.5 47.5 30–352 n/a 
ParameternMean ± SDMedianRangeNormal range
n/a, not applicable 
LIC, mg Fe/g dw 14 21.8 ± 11.0 23.5 3.8–40.5 <1.3 
Serum ferritin,μg/L 14 4645 ± 3804 3534.5 1433–15380 20–360 
Serum iron, μg/dL 14 205.9 ± 26.5 200 165.9–252.0 50–160 
Transferrin, mg/dL 14 143 ± 19 142.5 106–172 200–400 
Transferrin saturation, % 14 113.8 ± 8.5 114 95–124 15–50 
LPI, μmol/L 14 0.7 ± 0.7 0.6 0–1.9 
Num. of lifetime transfusions 14 106.3 ± 115.5 47.5 30–352 n/a 

Renal function: Calculated creatinine clearance at baseline was normal (>80 mL/min) in 46% of patients, mildly impaired (50–80 mL/min) in 46% and moderately impaired (30–50 mL/min) in 8% of patients. Hematological parameters: neutropenia (<1800/μL): 1 patient; thrombocytopenia (<100,000/μL): 3 patients; neutropenia and thrombocytopenia: 1 patient. Concurrent therapies: Revlimid: 2 patients; and hydroxyurea: 1 patient.

Conclusions: Baseline iron burden in these patients demonstrates a high degree of iron overload, as measured by LIC via MRI, as well as serum ferritin, serum iron and transferrin saturation. Based on NCCN guidelines for the management of iron overload, the degree of iron overload observed meets criteria for treatment. This ongoing study is assessing the safety and efficacy of deferasirox in this population.

Disclosures: B Kang, J Decker and C Paley are Novartis employees.; P Greenberg - Consultant to Novartis on several occasions in C Schiffer - Advisory boards for Novartis about CML (not Exjade).; P Greenberg - support from Novartis for two clinical trials using Exjade for MDS patients; C Koller - received research funding from Novartis for the study described in this abstract; C Schiffer - Clinical research grants from Novartis.; P Greenberg - for consulting; C Schiffer - for consulting and lectures.; P Greenberg - Novartis advisory committee for Exjade; C Schiffer - Advisory boards for Novartis about CML (not Exjade).

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