Thalidomide in beta-thalassemia – a systematic review and meta-analysis

Abstract Introduction. Beta-thalassemia, an inherited hemoglobinopathy, affects approximately 18 people per 100,000 worldwide. Severe cases can require regular transfusions to maintain a hemoglobin level compatible with life. Curative therapies such as allogeneic hematopoietic stem cell transplant and disease-modifying therapies such as Luspatercept have become standard of care. However, these treatments are often unavailable at the centers that treat these patients first-line. As a result, fetal hemoglobin (HbF) inducers have been used for their increased accessibility. In this study, we conducted a systematic review and meta-analysis to better understand the efficacy of thalidomide treatment for beta-thalassemia. Methods. We conducted a literature search across PubMed, Ovid Medline, SCOPUS, PMC, CINAHL, Cochrane CENTRAL, and ClinicalTrials.gov. Our inclusion criteria screened for 1) studies conducted prospectively or retrospectively, 2) patients of age 14 and older with diagnosis of beta-thalassemia, and 3) a thalidomide monotherapy treatment arm. Studies were excluded if they were case reports/series, reviews, conference abstracts, studies without full text availability, or if data were incomplete. Two independent reviewers screened all studies, with a third serving as a tiebreaker. Data on change in hemoglobin levels with thalidomide treatment was recorded and a within-group mean difference analysis was performed. Results. Six studies meeting our prespecified criteria were identified. Of these, five were single arm studies. Four of six were prospective studies. Cochran's Q was 58.53 (p<0.001), indicating presence of significant heterogeneity. Between-study variance (τ2) was 2.17 (95%CI: 0.72-15.0), with calculated standard deviation of true effect sizes (τ) of 1.47 (95%CI: 0.85-3.87) and I2 of 91.5% (95%CI: 84.2-95.4%). Pooled change in hemoglobin after thalidomide treatment using a random-effects model was 2.65 g/dL (95%CI: 1.01-4.29 g/dL). One instance of grade 3 syncope was noted. The remaining adverse effects (AEs) were grade 1-2, with the most common being somnolence (53/155 patients), constipation (28/155 patients), and vertigo (22/155 patients). Conclusion. In patients with beta-thalassemia, thalidomide treatment induced a significant increase in hemoglobin concentration. All AEs were grade 1-2 and did not require drug discontinuation. Our results suggest that in settings where gold standard therapies may be unavailable, thalidomide may be a promising treatment option for patients with beta-thalassemia.