Anaemia

Dual iron chelation an attractive alternative to monotherapy in thalassaemia


Dual iron chelation could be an effective, long-term solution to serum ferritin management and may even help with treatment-related liver toxicity in beta thalassaemia major patients, Australian haematologists suggest.

A real-world study of 18 patients on median 23 months’ deferasirox and deferoxamine found the combination helped reduce median serum ferritin levels and liver iron content by 42% (P = 0.004) and 76% (P = 0.062), respectively.

Though not statistically significant, the latter change occurred in most patients, with figures dropping from median 4 mg/g (range <1–23) to 2 mg/g (range <1–11), Monash Health haematologist Dr Ahmad Zargari and colleagues wrote in Vox Sanguinis.

“This may be because [dual chelation therapy] has been shown to be a means to quickly reduce [liver iron content] compared to cardiac iron”, they explained.

Dual therapy made little difference to cardiac iron load, reducing levels by median 8% (P = 0.657).

Despite the retrospective study’s small size and lack of statistical significance around cardiac and liver iron loading, the authors felt dual therapy was a promising alternative to monotherapies in terms of ferritin and adverse event management.

Tolerance

While Australians can access individual iron chelators, poor tolerance, degree of transfusional iron intake and pharmacokinetic variability between patients mean some users may not achieve ferritin control on therapies such as deferasirox or deferoxamine alone.

Additionally, patients on deferasirox may be more prone to gastrointestinal upsets, osteoporosis and liver and renal toxicities, while deferoxamine users may face local skin irritation and visual/auditory neurotoxicity.

With its “non-additive side-effect profile” and varying modes of iron reduction — either via the faecal route or kidneys, dual therapy is an “attractive option” for certain patients, the authors wrote.

“Combining therapies may provide improved iron excretion in patients in whom maintaining acceptable ferritin levels with monotherapy remains a challenge, and offers an alternative for patients intolerant to or plagued by adverse effects at adequate dosing with monotherapy,” they suggested.

The recommendation applies to paediatric and adult patients — where people aged four to 58 were included in the study and benefited from dual treatment over the two-months to six-years recorded in Monash Health’s thalassaemia database.

“The authors are unaware of other studies in patients receiving [dual chelating therapy] with [deferasirox] and [deferoxamine] for up to 6 years or showing efficacy in paediatric patients as young as 4 years,” Dr Zargari and co wrote.

“DCT over a prolonged period was observed as an effective method to reduce serum ferritin and possibly liver iron load in patients with beta thalassaemia major in the real-world hospital-based setting,” they concluded.

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