The challenges of handling deferasirox in sickle cell disease patients older than 40 years

Abstract

Objectives: Deferasirox is an oral iron chelator with established dose-dependent efficacy for the treatment of iron overload secondary to transfusion. However, there is few data reporting the use of Desferasirox in adult patients with sickle cell disease (SCD) and transfusional iron overload. Methods: We conducted a prospective, single center, nonrandomized study from January 2014 to March 2015 in Campinas, Brazil. Seven patients (five women, median age 50 y.o.) who were followed up on regular transfusion program were treated with a single daily dose of deferasirox (median dose 20 mg/kg). They were monitored for clinical symptoms, renal function and hepatotoxicity.Results: One patient discontinued the study due to lack of compliance. Two patients reported mild to moderate adverse events (gastrointestinal disturbances). Five patients had the drug discontinued due to worsening of renal function. One patient had the drug discontinued due to severe hepatotoxicity that evolved to death; no patient finished the study. Discussion and conclusions: Deferasirox does not appear to be well tolerated in SCD patients older than 40 years, in which complications of the underlying disease are already fully installed. The choice of the ideal iron chelator for this population should include an evaluation of comorbidities and organic dysfunctions, as well as the need to find pharmacogenetic safety markers in this group of patients.

Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study

“…15,16 Deferasirox is taken orally as tablets or granules, which provides convenience; however, the drug has been associated with hepatic, gastrointestinal, and renal toxicities, which is of particular concern for patients with SCD who may have preexisting renal impairment. 17 Deferiprone (Ferriprox, Chiesi USA, Cary, NC) is an oral iron chelator, available in tablet and liquid formulations, that is approved for the treatment of iron-overload in patients with thalassemia syndromes when other iron chelation therapy is inadequate. [18][19][20][21] Its long-term efficacy and safety in that population have been well studied, 9,22,23 but data in patients with SCD and other transfusion-dependent anemias are limited.…”

“… 15,16 Deferasirox is taken orally as tablets or granules, which provides convenience; however, the drug has been associated with hepatic, gastrointestinal, and renal toxicities, which is of particular concern for patients with SCD who may have preexisting renal impairment. 17 …”

New Deferric Amine Compounds Efficiently Chelate Excess Iron to Treat Iron Overload Disorders and to Prevent Ferroptosis

“…Although the recently approved chelator DFX has improved compliance compared to DFO and DFP, the oral administration of DFX also manifests significant adverse effects, such as gastrointestinal and renal toxicities. [ 17 ] Nonetheless, tremendous efforts are seen in the literature in developing different chemicals to coordinate with iron. [ 18 ] With the aim of developing more effective methods for delivering iron chelators, new chelators with greater therapeutic efficacy and less toxicity are very much needed.…”

ERFE regulation in sickle cell disease: complex but promising

“…For the moment, the best ways to manage IO in SCD remain a careful review of indications for RBC transfusions, which should be limited to when they are actually needed, and the use of iron chelators when IO is objectively demonstrated. However, the currently available iron chelators are far from optimal, particularly in SCD patients (Ribeiro et al , ), so that new therapeutic approaches are eagerly awaited. Indeed, ERFE represents a promising new therapeutic target.…”

“…However, the currently available iron chelators are far from optimal, particularly in SCD patients (Ribeiro et al, 2019), so that new therapeutic approaches are eagerly awaited. Indeed, ERFE represents a promising new therapeutic target.…”