ASH: Deferasirox Iron Chelation Associated with Reduced Mortality in Myelodysplastic Syndrome

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ATLANTA — Deferasirox (DFX) iron chelation therapy reduces mortality among patients with myelodysplastic syndrome (MDS), according to a retrospective cohort study presented during the 54th American Society of Hematology Annual Meeting and Exposition.

“The decrease in death was proportional to the duration of therapy,” reported lead author Amer M. Zeidan, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, MD. The study “lends significant support to a positive association of oral iron chelation therapy [ICT] with decreased mortality in MDS patients with a minimum transfusion threshold, and ongoing transfusion needs.”

Little is known about ICT's effects on MDS, so Dr. Zeidan and colleagues studied administrative Medicare claims database records for 4,060 patients diagnosed with MDS between 2005 and 2008. Patients were eligible if they had 2 outpatient or 1 inpatient ICD-9 code for MDS and 10 weeks of transfusion or 20 units of peripheral red blood cells. Exclusions included any acute myeloid leukemia prior to cohort entry or parenteral ICT after cohort entry.

Patients had a mean age of 77.7 years; 9.7% were non-white and 54% were female.

DFX was used during the observation period by 481 (11.8%) of patients, with a median duration of 20.5 weeks and a mean of 29.2 weeks,  the authors reported. Median follow-up was 34 weeks, 66 weeks for DFX-users vs 31 weeks for non-users.

A total of 2,390 of the 4,060 patients (58.9%) died during the observation period; median time to death was 27 weeks. The survival hazard ratio for DFX users vs non-users was 0.988 (0.982–0.994; P<0.001) per week DFX was administered. Median survival was 47 weeks for DFX non-users; for those who used DFX ≤13 weeks, median survival was 53 weeks; for 14-26 weeks of use, 91 weeks; for 27-52 weeks, 118 weeks; and, for patients receiving 53 or more weeks of DFX, median survival was not reached. Median survival for receipt of any DFX was 110 weeks. Cumulative transfusion, increasing age, and higher-risk MDS were associated with increased mortality.

DFX therapy was associated with a decrease in leukemic progression as well as endocrine and renal dysfunction; and with a trend, but not a statistically significant, reduction in incident congestive heart failure.

“This is the first large population-based Medicare study evaluating the association between DFX use in older MDS patients and sequelae of iron overload and mortality,” Dr. Zeidan noted, adding “unobserved factors that may influence physician selection of patients for ICT cannot be assessed in our model.”

Among MDS and elderly patients, deferasirox can cause life-threatening liver and kidney damage, and intestinal and gastric hemorrhage.  

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