Long-term clinical efficacy and safety of thalidomide in patients with transfusion-dependent β-thalassemia: results from Thal-Thalido study

Abstract

Regular blood transfusion is the mainstay of treatment in transfusion-dependent β-thalassemia (TDT); however, transfusions culminate in an array of serious complications. Therefore, a single-arm, non-randomized clinical trial was conducted in hydroxyurea refractory TDT patients to explore the long-term safety and efficacy of thalidomide. The primary outcomes for efficacy were rise in hemoglobin (Hb) level and changes in transfusion frequency. Whereas, several clinical and laboratory parameters were assessed for safety of thalidomide. Secondary outcomes included changes in serum ferritin, serum lactate dehydrogenase (LDH), serum uric acid, red blood cell indices, and size of liver and spleen. A total of 532 patients were followed for a period of 30 months. Significant increase in mean Hb level was identified at 6 months (1.4 g/dL, p ≤ 0.001) and 30 months (2 g/dL, p ≤ 0.001) in comparison with baseline. A total of 408 (76.7%) patients responded to thalidomide therapy (excellent responders 25.8%, good responders 31%, and partial responders 19.9%) and attained transfusion independence within 6 months of therapy. A significant decline in mean ferritin, LDH level, liver size, and spleen size was observed. No unfavorable effects were observed on kidney and liver functions. Mild adverse events were reported in 48 (9%) patients and serious adverse events, including cerebral vascular accident and portal vein thrombosis were reported in two patients each. This study concludes that thalidomide is an effective and well-tolerated drug that can improve Hb levels and reduce transfusion burden in hydroxyurea refractory TDT patients.Trial registration: This trial is registered at http://www.clinicaltrial.gov as # NCT03651102.

Secondary amenorrhea in a β‐thalassemia major patient treated with thalidomide

“…5 Among the previous studies, except for peripheral neurotoxicity, central venous thromboses, autoimmune hemolytic anemia, cerebrovascular accidents, and seizures in a few patients, the reported adverse effects were mild, and the common adverse effects included constipation, somnolence, arthralgias, and rashes. 3,[6][7][8] Hardly any report of secondary amenorrhea following thalidomide therapy have been reported in patients with β-thalassemia. Amenorrhea, as an adverse effect of thalidomide, was first reported in 1998 by Ordi et al 9 Amenorrhea during treatment with thalidomide is considered a rare side effect with a prevalence of 0.02%.…”