Background: Few studies have reported the efficacy of iron chelation therapy in transfusion-dependent rare anemias as most trials of iron chelators evaluated patients with β-thalassemia. The efficacy and safety of deferasirox in the management of iron overload in rare anemias was evaluated as part of the EPIC study, the largest prospective trial of any iron chelator, and are presented here.

Methods: Patients (pts) with various transfusion-dependent rare anemias were enrolled if they had serum ferritin (SF) levels of ≥1000 ng/mL, or <1000 ng/mL but with a history of multiple transfusions (>20 transfusion episodes or 100 mL/kg of blood) and R2 MRI-confirmed liver iron concentration >2 mg Fe/g dry weight. Initial deferasirox dose was 10–30 mg/kg/day depending on transfusion requirements. Dose adjustments in steps of 5–10 mg/kg/day (range 0–40 mg/kg/day) were based on SF trends and safety markers indicative of iron toxicity. SF was assessed every 4 weeks; the primary efficacy endpoint was change in SF from baseline at 12 months. Safety assessments included adverse event (AE) monitoring and assessment of laboratory parameters.

Results: 43 pts (20 males, 23 females; mean age 39.5 years) with rare anemias were enrolled. This diverse population included: red cell aplasia (n=20), hemolytic anemia (n=11), pyruvate kinase deficiency anemia (n=5), autoimmune hemolytic anemia (n=3), acute porphyria (n=2), congenital anemia (n=1), hereditary hemolytic anemia (n=1), and thrombocytopenia purpura (n=1). Median baseline SF was 3161 ng/mL and transfusion requirements were high at 153.0 mL/kg of blood in the year prior to enrollment. In total, 55.8% (n=24) of pts had received prior chelation therapy with deferoxamine (DFO), 11.6% (n=5) with combination DFO/deferiprone, and 2.3% (n=1) with deferiprone. A further 13 pts (30.2%) were chelationnaïve. At 12 months, there was a significant reduction in median SF from baseline (−832.0 ng/mL; P=0.0275) at an average actual deferasirox dose (±SD) of 18.57±5.60 mg/kg/day. This reduction occurred both in pts who received an actual mean dose of deferasirox ≥20– <30 mg/kg/day (−770.5 ng/mL; 4247.7 ng/mL [baseline]; n=17, P=0.4452; 0.52 mg/kg/day [average iron intake]) and in those who received an actual mean dose of deferasirox <20 mg/kg/day (−846.0 ng/mL; 2571.7 ng/mL [baseline]; n=26, P=0.0174; 0.47 mg/kg/day [average iron intake]). Overall, 70% of pts (n=30) completed the study. The primary reason for withdrawal was AEs (n=8, 19%); one person each discontinued because of consent withdrawal, unsatisfactory therapeutic effect, or for other reasons. There were two deaths during the study, judged by investigators to be non-treatment-related (one due to acute respiratory insufficiency and another to bladder tumor). The most common drug-related AEs (investigator-assessed) were: diarrhea (n=13, 30%), nausea (n=9, 21%), abdominal pain (n=6, 14%), fatigue (n=5, 12%), rash (n=4, 9%), upper abdominal pain (n=4, 9%), vomiting (n=4, 9%), abdominal distension (n=3, 7%), constipation (n=3, 7%) and dizziness (n=3, 7%). All were mild-to-moderate in severity. Eight pts (18.6%) had an increase in serum creatinine >33% above baseline and the upper limit of normal (ULN) on two consecutive visits; there were no progressive increases. Increase in alanine aminotransferase >10xULN on two consecutive visits occurred in one (2.3%) patient who had elevated levels at baseline.

Conclusions: One year’s treatment with deferasirox reduced SF in this population of regularly transfused pts with various rare anemias. Deferasirox was generally well tolerated with predominantly gastrointestinal and transient dermatological AEs, consistent with those observed in previous clinical trials, and no evidence of renal or liver function impairment in this patient group.

Disclosures: 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. Lin:Novartis: Honoraria, Speakers Bureau. Habr:Novartis: Employment. Domokos:Novartis: Employment. Hmissi:Novartis: Employment. Thein:Novartis: Honoraria, Research Funding, Speakers Bureau.

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