Clinical Observation of Luspatercept in Treatment of Chinese Adult β-thalassaemia Patients With TD β-thalassemia

Efficary and Safety of Luspatercept for Treatment of Anaemia in Transfusion-dependent β-thalassaemia in Southwest China

To assesse the efficacy and safety of luspatercept versus placebo in China patients with transfusion-dependent β-thalassaemia.

This was a prospective, multicenter, open-label, multicenter clinical study to observe the efficacy and safety of luspatercept in the treatment of adult patients with transfusion-dependent β-thalassemia in Chinese clinical practice.

Luspatercept has been approved for listing in China for the treatment of that requires regular infusion of red blood cells and red blood cell infusion ≤ 15 units/24 weeks β- Adult patients with thalassemia. The BELIEVE study enrolled 117 patients of Asian descent from Malaysia, Thailand, Taiwan, Australia, the United States, the United Kingdom, and Canada. Efficacy results similar to those in the global intention-to-treat population were observed in Asian patients with a baseline transfusion load of 6 to 15 units per 24 weeks. The results in the Asian population provide valuable reference for the safety and efficacy of luspatercept in the Chinese population.

Ten adult patients with β-thalassemia were enrolled in this study,divided into two groups (5 cases with transfusion burden<7.5 units/24 weeks, and 5 cases with transfusion burden 7.5-15 units/24 weeks).Luspatercept was given once subcutaneously every 3 weeks for 24 weeks in the treatment period, . Luspatercept was started at 1·0 mg/kg with titration up to 1·25 mg/kg, or reduction in the event of toxicity or excessive haemoglobin concentration increase. During the treatment, the hemoglobin of the patients before each injection of luspatercept was monitored, and the common adverse reactions (AE) were monitored.The primary end point was the percentage of the LTB and HTB group patients who had a reduction in the transfusion burden of at least 33% and reduce blood transfusion unit from baseline group.According to the judgment and practice of clinicians, the best supportive treatment, including blood transfusion, iron chelation therapy, and anti-infection treatment, should be provided for patients receiving luspatercept treatment. Thus，this clinical trial is going to further explore its efficacy and safety.

Inclusion Criteria:

1. ≥18 years old;
2. A clear diagnosis of transfusion-dependent β-thalassemia (including αβ mixed type) with red blood cell transfusion ≤15u within 24 weeks before enrollment (one unit of red blood cell in overseas clinical research is 200-350ml packed red blood cells, which should be converted according to Chinese clinical practice);
3. Voluntarily participate in the study and sign the informed consent;

Exclusion Criteria:

1. pregnant or lactating women;
2. Allergic to luspatercept and/or luspatercept for injection excipients;
3. Severe liver dysfunction: Liver enzymes (alanine aminotransferase ALT or aspartate aminotransferase AST) ≥ 3 times normal value.;
4. Severe renal injury: eGFR<30 ml/min/1.73m3 or end-stage renal disease;
5. heart disease, New York Heart Association (NYHA) class 3 or higher heart failure, or the need for treatment Severe arrhythmia, or recent myocardial infarction within 6 months;
6. The patient had uncontrolled hypertension;
7. Patients with a history of deep vein thrombosis or stroke within 24 weeks prior to enrollment.;
8. Treatment with ESA, luspatercept, thalidomide or hydroxyurea within 12 weeks before enrollment;
9. Any significant other medical condition, laboratory abnormality, or mental illness;
10. Investigators deemed enrollment inappropriate.