Abstract

Background: The prospective, 1-yr multicenter EPIC trial evaluated the efficacy and safety of once-daily oral deferasirox (Exjade®) in more than 1700 patients (pts) with transfusion-dependent anemias. Data were collected from each patient at enrollment, providing an insight into transfusion history, body iron burden, and the nature and success of previous chelation therapy in a large group of pts with iron overload previously treated with chelation therapy.

Methods: Enrolled pts were aged ≥2 yrs, had transfusion-dependent anemia and serum ferritin (SF) levels of ≥1000 ng/mL, or <1000 ng/mL with a history of multiple transfusions (>20 transfusions or >100 mL/kg of RBCs) and MRI-assessed liver iron concentration (LIC) >2 mg Fe/g dry weight (dw). Baseline assessments included transfusion history, previous chelation therapy, SF levels and LIC (if carried out) in the previous yr.

Results: 1744 pts (901 M, 843 F) were enrolled. Underlying anemias were: thalassemia major (TM; n=937), thalassemia intermedia (TI; n=84), myelodysplastic syndromes (MDS; n=341), aplastic anemia (AA; n=116), sickle cell disease (SCD; n=80), rare anemias (red cell aplasia and anemias mostly hemolytic in nature; n=43), Diamond-Blackfan anemia (DBA; n=14), and various other conditions associated with anemias requiring transfusion (n=129). Baseline characteristics for key underlying anemias are presented in Table 1. Median SF levels were >2500 ng/mL and mean LIC in the previous yr was >7 mg Fe/g dw in all groups (except DBA for SF levels). MDS pts had received the most transfusions in the previous yr, although they had also spent a smaller proportion of their lifetime, and less total time, receiving transfusions than any other cohort. Together with AA pts, the MDS cohort also contained the highest proportion of pts who were chelation-naïve (68% and 48%). SCD pts were the least-transfused group in terms of amount of blood given, but had been receiving transfusions for more than 13 yrs. As expected, TM pts had spent the greatest proportion of their lifetime on transfusions and received the greatest volume of blood per kg in the previous yr. The group labeled by investigators as TI were relatively heavily transfused for this patient population.

Table 1. Baseline characteristics for key underlying anemias

 All (n=1744) TM (n=937) TI (n=84) MDS (n=341) AA (n=116) SCD (n=80) Rare (n=43) DBA (n=14) 
*Mean ± SD; **Median 
Age, yrs* 30.6±23.3 18.4±10.8 19.2±14.4 67.9±11.4 33.3±17.1 23.9±13.2 39.5±22.7 17.3±13.2 
Transfusions in last yr* 17.8±12.5 17.5±8.8 13.5±7.1 24.3±17.7 12.5±13.0 10.7±8.2 21.0±18.7 19.0±18.7 
Total transfused in last yr, mL/kg* 159±136 190±139 155±87 116±123 116±179 84±57 153±142 185±148 
Total yrs on transfusions* 12.3±10.4 16.8±10.4 10.2±7.8 3.6±4.6 6.1±5.7 13.0±9.6 10.9±11.8 13.3±10.0 
% of lifetime on transfusions* 62.9±39.4 89.8±15.2 61.2±28.8 5.7±8.4 27.1±29.3 59.5±30.1 44.3±41.5 87.5±23.2 
LIC in last yr, mg Fe/g dw* 10.7±9.0 9.5±7.8 9.7±5.5 14.4±8.5 12.0±4.3 11.8±8.4 – 8.8±4.2 
SF, ng/mL** 3135 3157 3493 2730 3254 3163 3161 2289 
Prior chelation, %         
DFO 58.6 66.7 78.6 40.2 26.7 62.5 55.8 71.4 
Deferiprone 1.6 1.3 – 4.1 – 1.3 2.3 – 
DFO/deferiprone 16.7 25.0 4.8 7.0 5.2 12.5 11.6 14.3 
Other 0.3 0.4 – 0.3 – – – – 
None 23.0 7.0 16.7 48.4 68.1 23.8 30.2 14.3 
 All (n=1744) TM (n=937) TI (n=84) MDS (n=341) AA (n=116) SCD (n=80) Rare (n=43) DBA (n=14) 
*Mean ± SD; **Median 
Age, yrs* 30.6±23.3 18.4±10.8 19.2±14.4 67.9±11.4 33.3±17.1 23.9±13.2 39.5±22.7 17.3±13.2 
Transfusions in last yr* 17.8±12.5 17.5±8.8 13.5±7.1 24.3±17.7 12.5±13.0 10.7±8.2 21.0±18.7 19.0±18.7 
Total transfused in last yr, mL/kg* 159±136 190±139 155±87 116±123 116±179 84±57 153±142 185±148 
Total yrs on transfusions* 12.3±10.4 16.8±10.4 10.2±7.8 3.6±4.6 6.1±5.7 13.0±9.6 10.9±11.8 13.3±10.0 
% of lifetime on transfusions* 62.9±39.4 89.8±15.2 61.2±28.8 5.7±8.4 27.1±29.3 59.5±30.1 44.3±41.5 87.5±23.2 
LIC in last yr, mg Fe/g dw* 10.7±9.0 9.5±7.8 9.7±5.5 14.4±8.5 12.0±4.3 11.8±8.4 – 8.8±4.2 
SF, ng/mL** 3135 3157 3493 2730 3254 3163 3161 2289 
Prior chelation, %         
DFO 58.6 66.7 78.6 40.2 26.7 62.5 55.8 71.4 
Deferiprone 1.6 1.3 – 4.1 – 1.3 2.3 – 
DFO/deferiprone 16.7 25.0 4.8 7.0 5.2 12.5 11.6 14.3 
Other 0.3 0.4 – 0.3 – – – – 
None 23.0 7.0 16.7 48.4 68.1 23.8 30.2 14.3 

Conclusions: Data from this study population show that, although most pts with thalassemia, SCD, DBA and rare anemias had received previous chelation therapy, LIC and SF levels were above levels associated with significant negative outcomes (>7 mg Fe/g dw and >2500 ng/mL, respectively), which suggests that previous chelation practices were sub-optimal. Many pts with MDS and AA were chelation-naïve despite being heavily iron overloaded, highlighting that the risks of iron overload are still underestimated. These data highlight the need to carefully monitor iron levels in pts at risk of iron overload and initiate chelation therapy to avoid serious clinical sequelae.

Disclosures: Cappellini:Novartis: Speakers Bureau. Gattermann:Novartis: Honoraria, Participation in advisory boards on deferasirox clinical trials (Novartis). Viprakasit:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; GPO-L-ONE: Research Funding. Porter:Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Vifor International: Membership on an entity’s Board of Directors or advisory committees; Mundipharma: Membership on an entity’s Board of Directors or advisory committees. Kattamis:Novartis: Consultancy, Honoraria, Speakers Bureau. Li:Novartis: Consultancy, Speakers Bureau. Habr:Novartis: Employment. Domokos:Novartis: Employment. Hmissi:Novartis: Employment.

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