What is the treatment for Beta-Thalassemia (Beta-Thalassemia)

From the Guidelines

Thalassemia patients should be treated with regular blood transfusions and iron chelation therapy, with deferoxamine being the most effective chelating agent, as evidenced by its ability to increase survival and decrease cardiac complications in transfusion-dependent iron-overloaded thalassemia patients 1. When considering treatment options for thalassemia, it's essential to prioritize the management of iron overload, which is a significant complication of regular blood transfusions.

• Regular blood transfusions are the cornerstone of treatment for moderate to severe thalassemia major or intermedia, aiming to maintain hemoglobin levels above 9-10 g/dL.
• Iron chelation therapy is crucial to prevent iron overload, with deferoxamine being a highly effective option, as it has been shown to remove cardiac iron by direct interaction with the trivalent ferric ion 1.
• Deferoxamine therapy has been associated with increased survival and decreased cardiac complications in transfusion-dependent iron-overloaded thalassemia patients, making it a preferred choice for iron chelation therapy 1.
• Other chelating agents, such as deferasirox and deferiprone, may also be considered, but their long-term efficacy and safety are not as well established as deferoxamine 1.
• Comprehensive care, including vaccinations, regular monitoring for complications, and psychological support, is also essential for thalassemia patients.
• Stem cell transplantation and gene therapy are emerging treatments that may offer a potential cure for eligible patients.

From the FDA Drug Label

The primary efficacy study, Study 1 (NCT00061750), was a multicenter, open-label, randomized, active-comparator control study to compare deferasirox tablets for oral suspension and deferoxamine in patients with beta-thalassemia and transfusional hemosiderosis Patients greater than or equal to 2 years of age were randomized in a 1:1 ratio to receive either oral deferasirox tablets for oral suspension at starting doses of 5,10,20, or 30 mg per kg once daily or deferoxamine at starting doses of 20 to 60 mg per kg for at least 5 days per week based on LIC at baseline Reduction of LIC and serum ferritin was observed with deferasirox tablet for oral suspension doses of 20 to 30 mg per kg per day. Therefore, a starting dose of 20 mg per kg per day is recommended [see Dosage and Administration (2. 1)].

To treat Thalasemia, the recommended starting dose of Deferasirox is 20 mg per kg per day. The treatment should be based on the patient's Liver Iron Concentration (LIC) at baseline. Deferasirox has been shown to reduce LIC and serum ferritin levels in patients with beta-thalassemia and transfusional hemosiderosis 2. Key points to consider:

• Starting dose: 20 mg per kg per day
• Dose adjustment: based on LIC at baseline
• Patient population: patients with beta-thalassemia and transfusional hemosiderosis
• Efficacy: reduction of LIC and serum ferritin levels.

From the Research

Treatment Options for Thalassemia

• Thalassemia major can be cured through regular transfusion of blood, transplantation of bone marrow, iron chelation management, hematopoietic stem cell transplantation, stimulation of fetal hemoglobin production, and gene therapy 3
• Thalassemia intermediate treatment is symptomatic and can also be accomplished by folic supplementation and splenectomy 3

Iron Chelation Therapy

• Iron chelation therapy is used to remove accumulated iron and detoxify iron, which can prevent and reverse much of the iron-mediated organ injury 4
• Three chelators are commercially available: deferoxamine, deferasirox, and deferiprone, and each can be used as monotherapy or in combination 4
• Close monitoring of hepatic and cardiac iron burden is central to tailoring chelation 4
• Combination chelation often is employed for patients with high iron burden, iron-related organ injury, or where adverse effects of chelators preclude administration of an appropriate chelator dose 4

Optimizing Iron Chelation Strategies

• Iron chelation therapy should be tailored to the individual patient, based on the transfusional iron loading rate and the current level of iron load both intra- and extra-hepatically 5
• Deferoxamine, deferasirox, and deferiprone are commonly used iron chelators, and recent advances in the use of deferasirox have shown efficacy with an acceptable safety profile in adults and children 5
• Recent evidence suggests that deferasirox up to 30 mg/kg/day can be safely administered to patients with serum ferritin levels between 500 and 1000 mg/L, while doses above 30 mg/kg/day can be given to patients with substantial iron overload or with high transfusion rates 5

Clinical Challenges with Iron Chelation

• Inadequate iron chelation therapy continues to contribute to preventable morbidity and mortality in transfusion-dependent thalassemia 6
• Factors that contribute to suboptimal iron chelation include poor adherence, variable pharmacokinetics, chelator adverse effects, and difficulties with precise monitoring of response 6
• The regular assessment of adherence, adverse effects, and iron burden with appropriate treatment adjustments is necessary to optimize patient outcomes 6

Effect of Iron Chelation Regimens on Bone Mass

• Iron overload might lead to bone loss in transfusion-dependent beta-thalassemia patients, and iron chelation therapy can help improve bone mass 7
• Combination therapy with deferoxamine and deferasirox had the highest impact on reducing serum ferritin and improving bone loss in both lumbar spine and femoral neck 7