Deferasirox for the treatment of iron overload in non-transfusion-dependent thalassemia

Abstract

Non-transfusion-dependent thalassemia (NTDT) defines a group of patients who do not require regular transfusions for survival, but are at significant risk of iron accumulation from underlying disease-related mechanisms distinct from transfusional iron overload. Management of iron overload in NTDT has received little attention compared with that of β-thalassemia major, despite evidence of significant iron-induced complications with advancing age. The efficacy and safety of the iron chelator deferasirox in NTDT has been evaluated in two pilot studies and the first prospective, randomized, placebo-controlled study (THALASSA) of any chelator in NTDT. Treatment with deferasirox for up to 2 years yielded a sustained reduction in iron burden, with a clinically manageable safety profile. Following these trial data, deferasirox is the first iron chelator approved for use in NTDT patients, and with NTDT guidelines now available, physicians are better equipped to achieve effective monitoring and management of iron burden in NTDT.

Keywords::

• deferasirox
• iron chelation
• iron overload
• thalassemia

Financial & competing interests disclosure

AT Taher received research funding and honoraria from Novartis Pharmaceuticals. MD Cappellini reports participating in a Novartis Pharmaceuticals speaker’s bureau and receiving honoraria from Novartis and Genzyme. The authors are fully responsible for the content and editorial decisions for this manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. The authors thank Michelle Utton-Mishra, Mudskipper Business Ltd, for medical editorial assistance with this manuscript.

Key issues

• • Deferasirox (Exjade®) is a once-daily tridentate chelator with proven efficacy in the treatment of transfusional iron overload.

• • The efficacy and safety of deferasirox in non-transfusion-dependent thalassemia (NTDT) patients has been established in pilot studies, and subsequently in the first large prospective study of an iron chelator in the NTDT population, the THALASSA study.

• • Across studies spanning up to 2 years of treatment, deferasirox was associated with a significant reduction in iron burden in NTDT patients, as measured by liver iron concentration and serum ferritin.

• • The safety profile of deferasirox in NTDT is generally consistent with previous reports, with manageable gastrointestinal events comprising the majority of treatment-related adverse events.

• • Regular monitoring and clinical management, including laboratory tests of renal and hepatic function, is required for all patients undergoing treatment with deferasirox.

• • Deferasirox is the first iron chelator to gain approval for the treatment of iron overload in NTDT patients.

• • Data from the THALASSA study support current prescribing recommendations for deferasirox and have served as a fundamental basis for the development of guidelines on chelation therapy in NTDT patients.

Notes