Deferasirox (Exjade^®) Treatment of Chelation-Naive and Pre-Chelated MDS Patients with Transfusional Iron-Overload in the Medical Practice:Results From the Observational Studies Extend and Exjange.

Red blood cell (RBC) transfusions on a regular basis are unavoidable in a variety of chronic anemias. Unfortunately, chronic transfusion therapy leads to iron overload (IOL) since the body cannot actively remove excess iron. Transfusional IOL can cause severe organ damage, as exemplified by thalassemia major patients in the past. Many patients (pts) with myelodysplastic syndromes (MDS) also need regular RBC transfusions and are thus threatened by secondary hemochromatosis. Deferasirox (Exjade^®), an oral iron chelator taken once-daily, has been shown in several clinical trials to maintain or reduce body iron (assessed by liver iron concentration [LIC] or serum ferritin [SF]) in pts with transfusion-dependent IOL. Here we summarize the results of two post-marketing surveillance studies of previously unchelated (Extend; n=123) and pre-chelated (Exjange; n=44) MDS pts with IOL. Pts were analyzed in the daily-routine setting of office-based physicians.

The Extend and Exjange observation studies cover 1 year of chelation treatment of iron overloaded, transfusion-dependent MDS pts. Deferasirox was prescribed in accordance with the terms of Exjade marketing authorization in Germany (Fachinformation). No inclusion or exclusion criteria or additional diagnostic or monitoring procedures were applied. Hematological parameters, including SF, and adverse events (AEs) were collected in 2-monthly intervals.

123 MDS pts (65 M, 58 F; mean age 70.4, range 17.6-90.3 yrs) with a median baseline SF of 2679 (range 184-16500) ng/mL without prior chelation and 44 MDS pts (24 M, 20 F; mean age 69.6, range 42.5-88.5 yrs) with a median baseline SF of 2442 (range 521-8565) ng/mL, mainly pre-chelated with Desferal, were observed. The mean prescribed daily dose of deferasirox at the first visit was 15.7 and 18.7 mg/kg/d, respectively. During treatment, median SF levels clearly decreased from first to final visit [-662.3 ng/ml; p<0.0002 (explorative analysis)] in the chelation-naïve and also in the pre-chelated MDS population [-716.0 ng/ml; p<0.0634 (explorative analysis)]. 64.2% of the Extend MDS pts and 47.7% of the Exjange MDS pts completed the 12 months observation period. Reasons for discontinuation included AEs in 19.5% (n=24) and 25% (n=11), respectively. The most common investigator-assessed drug-related AEs were diarrhea (n=13, 10.6% and n=4, 9.1%), nausea (n=11, 8.9% and n=1, 2.3%), and skin reactions (n=8, 6.5 % and n=2, 4.6%), mainly of mild-to-moderate severity. As in previous clinical trials, serum creatinine values showed a minor increase over the study period (median increase until final visit: 0.2 mg/dL in the Extend and 0.1 mg/dL in the Exjange study).

With deferasirox treatment, SF levels declined significantly over the 1-yr observation period in chelation-naïve MDS pts. A similar reduction was also observed in pre-chelated MDS pts. The safety profile of deferasirox was comparable to that previously reported in clinical trials, with mild-to-moderate diarrhea being the most common drug-related AE. Thus, deferasirox is an effective and safe iron chelator for the treatment of IOL in transfusion-dependent MDS pts in the daily-routine situation. The fact that median baseline levels of SF were around 2500 ng/ml in both the Extend and Exjange studies indicates that in everyday clinical practice MDS patients are started relatively late on iron chelation therapy and tend to be inadequately treated with Desferal.

Gattermann:Novartis: Honoraria, Participation in Advisory Boards on deferasirox clinical trials. Leismann:Novartis: Employment. Nass:Novartis: Employment. Germing:Novartis: Honoraria, Research Funding.