Patients with sickle cell disease (SCD) or other anemias treated with the iron chelator deferiprone showed progressive reduction in iron load, according to the results of the FIRST-EXT study published in Blood Advances.
Repeated blood transfusions, which is common in SCD, can cause iron overload. Deferiprone is an approved iron chelator for thalassemia syndromes, SCD, and other transfusion-dependent anemias; however, the long-term efficacy and safety data in SCD and other anemias are limited. The aim of this extension trial was to evaluate long-term safety, tolerability, and efficacy of deferiprone in this population.
The multicenter, single-arm, open-label FIRST-EXT study is an extension study of FIRST, in which patients with SCD were randomly assigned to receive deferiprone or deferoxamine.
In the extension study, 134 patients continued or switched treatment to deferiprone for a mean of 2.1 years. The primary endpoint was safety and secondary endpoints included, change in liver iron concentration (LIC), cardiac T2*, serum ferritin (SF), and response rate.
The median age of patients in the extension study was 14, 39.6% were female, and 14.9% were Black. SCD was present among 85.8% of patients and the most common other anemias were hereditary spherocytosis among 6%, and congenital dyserythropoietic anemia and spherocytic anemia among 3% each. The baseline LIC was 14.93 mg/g, SF was 3894 μg/L, and cardiac T2* was 32.69 ms.
The response rate to deferiprone increased over time, with rates of 46.5% in year 1 to 66.1% in year 3 for LIC and 35.2% and 70.9%, respectively, for SF.
There was also a progressive improvement in markers of iron load. The mean change from baseline of LIC was -2.64 in year 1 (P <.0001) and -6.64 in year 3 (P <.0001). SF was significantly lower than baseline beginning in year 2, with a mean change of -771 (P =.008) and progressively decreased to -1016 in year 3 (P =.042).
There were no new safety signals and cardiac T2* remained normal in all patients. Overall, 30.6% of patients experienced an adverse event that was possibly related to treatment, with the most common including neutropenia at 9.0% and abdominal pain at 7.5%.
Due to sufficient data for efficacy and safety, the FIRST and FIRST-EXT studies were stopped early after recommendation by the Data Safety Monitoring Board. The authors concluded that “deferiprone progressively decreased body iron load for up to 3 years of treatment in patients with SCD and other transfusion-dependent anemias.”
Disclosures: This study was supported in part by Chiesi Canada Corp. Please see the original reference for a full list of disclosures.
Elaalfy MS, Hamdy M, El-Beshlawy Am et al. Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years. Blood Adv. 2023;7:611-619. doi: 10.1182/bloodadvances.2021006778