Among patients with transfusion-dependent beta-thalassemia (TDT), thalidomide appears to be a promising therapy, according to data from a randomized trial published in Signal Transduction and Targeted Therapy.

Beta-thalassemia is among the most common heritable blood disorders in the world. The disease is defined by impaired hemoglobin synthesis and erythropoiesis, as well as premature red blood cell rupture.

While many patients do not require long-term transfusion, as many as 26,000 patients of those diagnosed each year will develop TDT. There is, furthermore, evidence that as few as 12% of pediatric patients with TDT receive adequate blood transfusion, and less than 40% receive adequate iron chelation therapy. Stem cell transplantation, which may be curable, is, furthermore, available to less than one-third of patients, and has a treatment-related mortality rate of up to 10%.

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Although some novel therapies, including gene therapy, have shown promise in this setting, there is evidence that older drugs, including thalidomide, may be effective in this patient population. For this randomized, placebo-controlled phase 2 study, researchers evaluated the safety and efficacy of thalidomide in patients with TDT.

Of the 107 patients assessed for study eligibility, 50 were randomly assigned to receive thalidomide, while 50 were assigned to receive placebo. In the overall cohort, the average age was 18.4 years, 60% of patients were male sex, the mean hemoglobin levels were 71.4 g/L, and the average number of red cells transfused over the preceding year was 42.8 U.

Patients in the thalidomide group had a median hemoglobin elevation of 14.0 g/L (range, 2.5-37.5), while no change was noted in the placebo group. Over a 12-week period, the mean red blood cell transfusion volume was lower in the thalidomide group (5.4 U) than in the placebo group (10.3 U; P <.001).

The authors also noted that particular patient genotypes, including non beta0/beta0 and HBS1L-MYB, predicted a response.

Patients in the thalidomide group were more likely to develop grade 1 to 2 dizziness (P =.016), drowsiness (P =.057), nausea (P =.051), and rash (P =.071) than were patients in the placebo group.

In an extension phase of the study, patients who received thalidomide for 24 weeks had sustainable hemoglobin concentration increases without blood transfusion.

“A phase III clinical trial is desired to further determine the safety and efficacy of thalidomide in TDT,” the authors wrote.


Chen JM, Zhu WJ, Liu J, et al. Safety and efficacy of thalidomide in patients with transfusion-dependent β-thalassemia: a randomized clinical trial. Signal Transduct Target Ther. 2021;6(1):405. doi:10.1038/s41392-021-00811-0