EFFICACY AND SAFETY OF THALIDOMIDE IN PATIENTS WITH TRANSFUSION-DEPENDENT β-THALASSEMIA: A SYSTEMATIC REVIEW, META-ANALYSIS AND GRADE EVALUATION

Background: The immunomodulatory drug thalidomide is a promising alternative therapy for transfusion-dependent β-thalassemia (TDT) due to its potent induction of fetal hemoglobin. Objective: To identify the efficacy and safety of thalidomide in TDT patients. Methods: A comprehensive search was conducted across MEDLINE, EMBASE, CENTRAL, Web of Science, CBM, CNKI, VIP, Wangfang Data, and OpenGrey, up to January 24, 2026. We included RCTs and observational studies involving more than 10 TDT patients treated with thalidomide for at least 3 months. Risk of bias was assessed using RoB 2 and MINORS tools. The certainty of evidence was evaluated with the GRADE approach. Results: Twenty-six studies involving 2422 patients were included. No studies had a high risk of bias. The meta-analysis of RCTs demonstrated that, compared with the control group, thalidomide significantly increased the major response rate (MRR; low certainty), the overall response rate (ORR; low certainty), and hemoglobin level (Hb; moderate certainty), as well as fetal hemoglobin level (HbF; moderate certainty). There was no significant between-group difference in changes in serum ferritin (SF) levels (very low certainty). The pre-post meta-analysis showed the following pooled outcomes: MRR 62.91% (very low certainty), ORR 75.07% (very low certainty), a Hb level change of 1.94 g/dL, a HbF level change of 39.21%, and an SF level change of -1432.39 ng/mL. The pooled incidence of adverse drug events (ADEs) was 4.65 per 100 person months, and that of ADEs leading to drug discontinuation was 0.04 per 100 person months. Most reported events were mild and tolerable. Conclusion: Thalidomide may provide limited benefits for TDT patients. In clinical practice, its potential risks must be thoroughly weighed against these benefits. Therefore, future large-scale, globally diverse, and high-quality RCTs are warranted.