Abstract

Introduction: Recent reviews indicate that transfusional hemosiderosis may be associated with an increased risk of mortality in lower-risk pts with MDS. This trial is designed to evaluate the efficacy and long-term safety of deferasirox (Exjade®, ICL670) in MDS. Deferasirox is an oral iron chelator approved for use in pts with transfusional iron overload.

Methods: This is a Phase II, open-label, 3-yr clinical trial in 55 US centers, enrolling 150 pts (aged ≥18 years) with Low- or Int-1-risk MDS (by IPSS criteria) and transfusional iron overload (serum ferritin ≥1000 ng/mL and >20 units RBC transfusions). Deferasirox dosing is 20–30 mg/kg/day. Serum ferritin, iron, transferrin and transferrin saturation are being assessed at screening and monthly in yr 1, then quarterly in yrs 2 and 3, while labile plasma iron (LPI) is assessed quarterly in yr 1. In addition, creatinine, calculated creatinine clearance, echocardiograms and endocrine and hematological status are being assessed. This report describes baseline data in these pts.

Results: As of June 2006, 84 pts have enrolled. Demographic data are available from 79 pts: median age 71 years (range 47–87); sex (52 male, 27 female); ethnicity (74 Caucasian, 2 Black, 2 Hispanic, 1 Oriental); and IPSS Risk Group (Low: 22 pts; Int-1: 56 pts). Iron status is summarized in the table:

ParameternMean ± SDMedianRangeNormal range
n/a, not applicable 
Serum ferritin,μg/L 84 3779 ± 4070 2951 1160–36280 12–370 
Serum iron, μg/dL 84 205 ± 64 201 48–409 37–180 
Transferrin, mg/dL 82 153 ± 31 152 83–244 190–375 
Transferrin saturation, % 83 85 ± 15 91 20–94 15–50 
LPI, μmol/L 38 0.52 ± 0.63 0.25 0–2.9 
Total transfusions, n 78 63.3 ± 66.3 41.5 14–435 n/a 
Years of transfusion 75 3.4 ± 1.9 1–12 n/a 
ParameternMean ± SDMedianRangeNormal range
n/a, not applicable 
Serum ferritin,μg/L 84 3779 ± 4070 2951 1160–36280 12–370 
Serum iron, μg/dL 84 205 ± 64 201 48–409 37–180 
Transferrin, mg/dL 82 153 ± 31 152 83–244 190–375 
Transferrin saturation, % 83 85 ± 15 91 20–94 15–50 
LPI, μmol/L 38 0.52 ± 0.63 0.25 0–2.9 
Total transfusions, n 78 63.3 ± 66.3 41.5 14–435 n/a 
Years of transfusion 75 3.4 ± 1.9 1–12 n/a 

Baseline concurrent therapies: 5-azacytidine (Vidaza): 5 pts; lenalidomide (Revlimid): 1 pt. Calculated creatinine clearance: normal (>80 mL/min): 37 pts; mildly abnormal (51–80 mL/min): 30 pts; moderately abnormal (30–50 mL/min): 9 pts. Hematological parameters: Anemia was present in all pts; other cytopenias included: neutropenia (<1800/μL): 13 pts, thrombocytopenia (<100,000/μL): 15 pts; neutropenia and thrombocytopenia: 12 pts. A total of 53 pts had received chelation prior to enrolling: 51 deferoxamine (Desferal®); and 2 deferasirox.

Conclusions: Despite the prior availability of deferoxamine, these baseline data demonstrate significant levels of iron overload among transfused pts with myelodysplasia. Serum iron, ferritin and LPI are all well above the clinically significant thresholds associated with increased complications. Since recent data has suggested that iron overload may be a poor prognostic indicator in MDS, increased attention to maintaining appropriate iron balance is warranted. The recent availability of an oral iron chelator may be more acceptable to MDS pts and their physicians. This ongoing trial is designed to assess the long-term efficacy, safety, and clinical benefits of deferasirox in pts with MDS.

Disclosures: J Esposito, J Decker and C Paley are Novartis employees.; A Raza - Advisory board for Novartis; A List - for Scios, Celgene, Pharmion, Kanisa, Schering.; B Powell - reported study supported in part by industry; D Steensma - funding to Mayo Clinic for clinical trials and ancillary studies in which he is involved: Novartis Oncology, MGI Pharma, OBIUS, Amgen; SL Goldberg - trial support of this abstract; A Raza - Clinical trial of Exjade in MDS; A List - for Scios.; SL Goldberg - Speakers’ bureau; A Raza - Speakers’ bureau; A List - From Celgene, Pharmion.; A Raza - Speakers’ bureau and advisory board; A List - With Scios, Celgene, Pharmion, Kanisa, Schering.

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