P1511: EFFICACY AND SAFETY OF COMBINATION IRON CHELATION THERAPY WITH DEFERIPRONE AND DEFERASIROX IN PATIENTS WITH Β-THALASSEMIA MAJOR: A SYSTEMATIC LITERATURE REVIEW

Abstract

Background: Iron overload can occur in patients with thalassemia syndromes because of hyperabsorption and/or frequent blood transfusions. Currently, 3 iron chelators are approved for clinical use: deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX). Combination iron chelation therapy may be prescribed for patients who do not adequately respond to monotherapy, have increased heart and/or liver iron overload, or have dose-dependent toxicity. It is important to optimize chelation to reduce iron-associated morbidity and early mortality and to improve quality of life. Oral DFP is typically administered as a monotherapy or in combination with DFO or DFX. Combination therapy was approved for clinical use by the European Medicines Agency in 2016; additionally, a recent British Society for Haematology guideline states that DFP+DFX is a highly effective combination therapy, although the safety and efficacy of DFX in combination with other iron chelators is not well established. Aims: A systematic literature review was conducted to evaluate the efficacy and safety profile of combination chelation therapy with DFP+DFX in patients with transfusion dependent β-thalassemia major (TDT). Methods: A systematic search was performed of the Embase and MEDLINE databases to identify trials related to the use of combination iron chelation therapy (DFP+DFX) in patients with TDT. The literature search was conducted in May 2021 and was not restricted to a specific start date. The search strings were established by logical association of appropriate words and MESH terms. The publications were screened based on a priori exclusion and inclusion criteria (eg, case-report exclusion). Results: Eight clinical study publications (7 prospective, 1 retrospective) of 1725 screened articles assessed the DFP+DFX combination for a total of 181 patients (Table). One publication was a pharmacokinetic (PK) study. Of the 7 studies, 6 reported a consistent reduction in at least 1 of the 3 studied endpoints (serum ferritin, liver, and cardiac iron). The PK study reported an additive effect in the total iron excretion in comparison with monotherapy. The adverse events reported with DFP+DFX were consistent with what has previously been reported for DFP or DFX monotherapy; no new adverse events were observed. The most common adverse events across the 7 studies included gastrointestinal symptoms, elevation in alanine aminotransferase and/or aspartate aminotransferase, arthralgia or joint symptoms, an increase in creatinine levels, proteinuria, and red-colored urine. The numbers of patients reported with neutropenia and thrombocytopenia were low (neutropenia, n=7 patients; thrombocytopenia, n=8 patients); agranulocytosis was not observed. Two studies reported serious adverse events, of which 1 (acute cholecystitis) was related to treatment. Image:Summary/Conclusion: This systematic literature review suggests that DFP+DFX combination iron chelation therapy can be a highly effective therapeutic option for improving iron overload, with an acceptable tolerability profile. This review supports the safety and efficacy of the combination, as approved by the EMA. Limitations of this analysis include small sample size and nonrandomization in most studies.