Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials

Research output: Contribution to journalArticle


Treatment with melphalan-prednisone-thalidomide improves the outcome of patients with multiple myeloma and is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. A meta-analysis of data from individual patients (n=1680) in six randomized trials was performed, comparing the effects of melphalan-prednisone-thalidomide versus melphalan-prednisone. The main objective was to estimate the risk of serious adverse events and their impact on outcome. The primary endpoints were the 2-year cumulative incidence of grade 3-4 hematologic and non-hematologic toxicities. At least 75% of the grade 3-4 toxicities occurred during the first 6 months of treatment in both treatment groups. The cumulative incidence of grade 3-4 hematologic toxicities was higher in the melphalan-prednisone-thalidomide group than in the melphalan-prednisone group (28% versus 22%; HR 1.32, 95% CI 1.05-1.66) as was the cumulative incidence of non-hematologic toxicities (39% versus 17%, HR 2.78, 95% CI 2.21-3.50). Grade 3-4 non-hematologic toxicities were significantly increased in patients with poor Performance Status. Occurrence of grade 3-4 non-hematologic toxicities had a negative impact on both progression-free survival (HR 1.24, 95% CI 1.07-1.45) and overall survival, (HR 1.23, 95% CI 1.03-1.47). Besides toxicities, progression-free and overall survival were also negatively affected by advanced International Staging System stage, high creatinine levels and poor Performance Status. Age had a negative impact on survival as well. Although melphalan-prednisone-thalidomide improved outcome, it increased toxicities, especially non-hematologic ones. Serious non-hematologic toxicities, older age, poor Performance Status, and high creatinine levels negatively affected survival. (C) 2013 Ferrata Storti Foundation. This is an open-access paper. doi: 10.3324/haematol.2012.067058


  • Antonio Palumbo
  • Anders Waage
  • Cyrille Hulin
  • Meral Beksac
  • Sonja Zweegman
  • Francesca Gay
  • Peter Gimsing
  • Xavier Leleu
  • Pierre Wijermans
  • Gulsan Sucak
  • Sara Pezzatti
  • Brigitte Pegourie
  • Martijn Schaafsma
  • Monica Galli
  • Ingemar Turesson
  • Brigitte Kolb
  • Bronno van der Holt
  • Ileana Baldi
  • Jurgen Rolke
  • Giovannino Ciccone
  • Marc Wetterwald
  • Henk Lokhorst
  • Mario Boccadoro
  • Philippe Rodon
  • Pieter Sonneveld
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)87-94
Issue number1
Publication statusPublished - 2013
Publication categoryResearch