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 potency as a fetal hemoglobin inducer.

Objective

To identify the efficacy and safety of thalidomide in TDT patients.

Methods

A comprehensive search was conducted of MEDLINE, EMBASE, CENTRAL, Web of Science, China Biology Medicine, CNKI, VIP, Wangfang data and Opengrey through April 26th, 2025. We included studies with an RCT or observational design that reported treating more than 10 TDT patients with thalidomide for at least 3 months. The version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) and the Methodological Index for Non-Randomized Studies (MINORS) were applied to evaluate bias risk. The overall certainty of the effect estimates was assessed by the GRADE system.

Results and Conclusion

Twenty-one studies and 1880 patients were included. None of the studies had a high risk of bias. Our study showed MRR (100% reduction in transfusion requirement) and ORR (≥ 50% reduction in transfusion requirement) rates of 63.87% and 72.32% respectively. Compared with controls, the thalidomide group showed statistically significant increases for both MRR and ORR (OR=20.40, 95% CI:6.75, 61.64). Thalidomide treatment significantly increased hemoglobin, and fetal hemoglobin levels while decreasing serum ferritin levels in TDT patients. The overall incidence rate of adverse drug events (ADEs) was 54.37%, and the incidence rate of ADEs leading to drug discontinuation was 1.12%. High-certainty evidence supported thalidomide’s clinical benefits: significantly higher MRR and ORR, and increased HbF levels compared to the controls.