title: Thalidomide treatment for patients with previously untreated multiple myeloma: a meta-analysis of randomized controlled trials.
abstract: The efficacy and safety of thalidomide as an initial treatment in myeloma patients who were unsuitable for autologous stem cell transplantation (ASCT), as induction treatment prior to ASCT, or as a maintenance treatment was unclear. The purpose of this study was to assess the benefits and risks of thalidomide for previously untreated myeloma patients. MEDLINE, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCTs) of thalidomide used in either induction or maintenance therapy for previously untreated myeloma patients. Twenty-two RCTs enrolling 9098 patients were identified, including 15 RCTs of induction thalidomide, 6 RCTs of maintenance thalidomide, and 1 RCT of induction and maintenance thalidomide. Induction thalidomide improved overall response rate (ORR) (risk ratio (RR) 1.54, 95 % confidence interval (CI) 1.30-1.83), complete response rate (CRR) (RR 3.03, 95 % CI 1.91-4.80), progression-free survival (PFS) (hazard ratio (HR) 0.65, 95 % CI 0.56-0.76), and overall survival (OS) (HR 0.78, 95 % CI 0.67-0.91) in patients who were not allowed to receive ASCT. Induction thalidomide improved pre-ASCT ORR (RR 1.20, 95 % CI 1.11-1.30), pre-ASCT and post-ASCT CRR (RR 1.47, 95 % CI 1.12-1.93 and RR 1.23, 95 % CI 1.00-1.50, respectively), and PFS (HR 0.73, 95 % CI 0.59-0.91) in patients who were allowed to receive ASCT, but it did not improve post-ASCT ORR (RR 1.04, 95 % CI 0.99-1.09) and OS (HR 0.91, 95 % CI 0.79-1.05). Improved PFS and prolonged OS were observed (HR 0.61, 95 % CI 0.53-0.70 and HR 0.77, 95 % CI 0.62-0.95, respectively) when thalidomide was added to maintenance therapy. More patients experienced venous thromboembolism (VTE) of grade 3/4 when thalidomide was added to induction or maintenance therapy (HR 2.15, 95 % CI 1.58-2.92 and RR 1.96, 95 % CI 1.13-3.40, respectively). Induction thalidomide still increased the risk of VTE (RR 1.53, 95 % CI 1.12-2.08) after VTE prophylaxis was used. Induction thalidomide effectively improved CRR, ORR, and PFS (except post-ASCT ORR). Notably, induction thalidomide improved OS in patients who were not allowed to receive ASCT but not in patients who were allowed to receive ASCT. The addition of thalidomide to maintenance therapy improved both PFS and OS. However, thalidomide led to a greater risk of VTE with grade 3/4. This risk did not disappear after VTE prophylaxis was used in induction therapy with thalidomide.
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China, 200072.
authors.forename: Minjie
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China, 200072.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China, 200072.
authors.forename: Houcai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China, 200072.
authors.forename: Bingqian
authors.initials: B
authors.lastname: Xie
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China, 200072.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China, 200072.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China, 200072.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa, IA, USA.
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.affiliation: College of life science and technology, Tongji University, Shanghai, China.
authors.forename: Bojie
authors.initials: B
authors.lastname: Dai
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China, 200072. taoyi018@139.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China, 200072. shijumei@tongji.edu.cn.
authors.forename: Jumei
authors.initials: J
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D013792:Thalidomide
keywords: Meta-analysis; Multiple myeloma; Thalidomide