Safety and efficacy of thalidomide in patients with transfusion-dependent β-thalassemia: a randomized clinical trial
Jiangming Chen, Weijian Zhu, Jie Liu, Guizhen Wang, Xiaoqin Chen, Yun Tan, Weiwei Xu, Li-Wei Qu, Jinyan Li, Huan-Ju Yang, Lan Huang, Ning Cai, Weida Wang, Ken Huang, Jian-Quan Xu, Guohui Li, Sheng He, Tian-Ying Luo, Yi Huang, Songhua Liu, Wenqiang Wu, Qiyang Lu, Mei-Guang Zhou, Shuying Chen, Rong-Lan Li, Meiling Hu, Ying Huang, Jinhua Wei, Junmin Li, Sai‐Juan Chen, Guang‐Biao Zhou
Abstract
Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.