A meta-analysis and systematic review of thalidomide for patients with previously untreated multiple myeloma

A systematic review and meta-analysis was performed to determine the efficacy and toxicity of thalidomide in previously untreated patients with myeloma. Medline, Embase, Cochrane Controlled Trials Register, and abstracts from the American Society of Hematology and the American Society of Clinical Oncology were searched for randomized controlled trials (RCTs) of either induction or maintenance thaticlomide in adults with previously untreated myetoma. Nine RCTs of induction thalidomide, three RCTs of maintenance thalidomide, and one RCT of induction and maintenance thalidomide were identified, involving a total of 4144 subjects. When thalidomide was added to standard, non-transptantation myetoma therapy, overall survival (CS) improved (HR 0.67; 95% CI 0.56-0.81). When thaliclomide was given as maintenance following autologous transplantation (ASCT), there was a trend to improved CS (HR 0.61, 95% CI 0.37-1.01); when the only trial which combined induction and maintenance thalidomide was excluded from this analysis, a significant survival advantage emerged (HR 0.49, 95% CI 0.32-0.74). The relative risk of venous thromboembotism (VTE) with induction thalidomide was 2.56 (95% CI 1.88-3.49). A meta-anatysis of trials/sub-groups administering low molecular weight heparin (LMWH) as VTE prophylaxis, suggested a persistently increased relative risk of VTE with induction thatidomide (RR 1.54, 95%CI 1.07-2.22). The relative risk of VTE was substantially lower, but still elevated, when thalidomide was given as maintenance therapy following ASCT (RR 1.95, 95% CI 1. 15-3.30). In summary, thalidomide appears to improve the overall survival of patients with newly diagnosed myetoma both when it is added to standard, non -transplantation therapy, and when it is given as maintenance therapy following ASCT. However, thalidomide is associated with toxicity, particularly a significantly increased risk of VTE. (c) 2008 Elsevier Ltd. All rights reserved.