Efficacy of Low Dose Vs Standard Dose of Thalidomide in Patients with Transfusion-Dependent Thalassemia (TDT): A Non-Inferiority Trial

Background Thalidomide has been demonstrated to induce global gene expression hereby increasing the proliferation of erythroid cells. Recent studies have revealed encouraging data regarding the efficacy and safety of thalidomide in both transfusion dependent (TDT) and non-transfusion dependent (NTDT) thalassemia. However, the optimal dose of thalidomide remains unclear. The study was designed to compare the efficacy and safety of thalidomide at low-dose (1 mg/kg/d) vs standard-dose (2 mg/kg/d). Methods Patients with TDT > 12 years of age with no recent (previous 6 months) intake of Hb enhancers were enrolled in a non-inferiority trial across 4 sites in India. Patients with hypersplenism, prior history of thromboembolism, HIV, active hepatitis B/C infection, or any other known systemic illness like neurological, renal, significant hepatopathy, and sexually-active females unwilling to use contraceptives/undergo medical termination of pregnancy in case of accidental pregnancy while on the drug were excluded. Patients were randomised to receive low-dose or standard-dose thalidomide for 6 months. Pre-transfusion Hb, transfusion frequency and volumes, and adverse effects were recorded at each visit. Response was graded based on reduction in transfusion requirement at 24 weeks: Good (> 50 %), moderate (25-50 %), or minimal (