Tumor Biology

, Volume 37, Issue 8, pp 11081–11098 | Cite as

Thalidomide treatment for patients with previously untreated multiple myeloma: a meta-analysis of randomized controlled trials

  • Minjie Gao
  • Yuanyuan Kong
  • Houcai Wang
  • Bingqian Xie
  • Guang Yang
  • Lu Gao
  • Yiwen Zhang
  • Fenghuang Zhan
  • Bojie Dai
  • Yi Tao
  • Jumei Shi
Original Article

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.

Keywords

Multiple myeloma Thalidomide Meta-analysis 

Abbreviations

RCTs

Randomized controlled trials

MM

Multiple myeloma

ORR

Overall response rate

CRR

Complete response rate

PFS

Progression-free survival

OS

Overall survival

ASCT

Autologous stem cell transplantation

HRs

Hazard ratios

CIs

Confidence intervals

VTE

Venous thromboembolism

ITT

Intention-to-treat

RRs

Risk ratios

Notes

Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (Nos. 81372391, 81300443, 31271496, 81570190, and 81529001) and Shanghai Tenth People’s Hospital Funds (No. 040113015).

Authors’ contributions

MJG and YYK designed this study, analyzed data, and drafted this manuscript. BQX and GY contributed to literature search and study selection. LG, YWZ, and BJD contributed to data collection and assessment of methodological quality. HCW, FHZ, JMS, and YT contributed to the interpretation of the results and revisions of the manuscript. All authors have read and approved the final manuscript.

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2016_4963_MOESM1_ESM.doc (40 kb)
Supplementary 1 Search criterion of Medline (via Pubmed, from inception to October 30, 2014) (DOC 40 kb)
13277_2016_4963_MOESM2_ESM.doc (44 kb)
Supplementary 2 Search criterion of Embase (from inception to November 06, 2014) (DOC 44 kb)
13277_2016_4963_MOESM3_ESM.doc (32 kb)
Supplementary 3 Search criterion of Cochrane Library (from inception to October 30, 2014) (DOC 32 kb)
13277_2016_4963_MOESM4_ESM.pptx (94 kb)
Supplementary 4 A sensitivity analysis of the effect of a single study of induction thalidomide in the absence of planned ASCT on the pooled overall survival. (PPTX 94 kb)
13277_2016_4963_MOESM5_ESM.pptx (98 kb)
Supplementary 5 A sensitivity analysis of the effect of a single study of induction thalidomide in the absence of planned ASCT on the pooled progression-free survival. (PPTX 98 kb)
13277_2016_4963_MOESM6_ESM.pptx (66 kb)
Supplementary 6 Begg’s funnel plots of the natural logarithm of the hazard ratios (HRs) and the SE of the natural logarithm of the HRs for all of the included studies that reported overall survival. The dashed line represents 95% confidence intervals (CIs). Circles represent individual studies. Begg’s test: p = 0.16. (PPTX 66 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Minjie Gao
    • 1
  • Yuanyuan Kong
    • 1
  • Houcai Wang
    • 1
  • Bingqian Xie
    • 1
  • Guang Yang
    • 1
  • Lu Gao
    • 1
  • Yiwen Zhang
    • 1
  • Fenghuang Zhan
    • 2
  • Bojie Dai
    • 3
  • Yi Tao
    • 1
  • Jumei Shi
    • 1
  1. 1.Department of Hematology, Shanghai Tenth People’s HospitalTongji University School of MedicineShanghaiChina
  2. 2.Department of Internal MedicineUniversity of Iowa, Carver College of MedicineIowaUSA
  3. 3.College of life science and technologyTongji UniversityShanghaiChina

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