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

Palumbo, Antonio; Waage, Anders; Hulin, Cyrille; Beksac, Meral; Zweegman, Sonja; Gay, Francesca; Gimsing, Peter; Leleu, Xavier; Wijermans, Pierre and Sucak, Gulsan, et al. (2013) In Haematologica 98(1). p.87-94
Abstract
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... (More)
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 (Less)
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Haematologica
volume
98
issue
1
pages
87 - 94
publisher
Ferrata Storti Foundation
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  • wos:000314107700020
  • scopus:84872055497
ISSN
1592-8721
DOI
10.3324/haematol.2012.067058
language
English
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yes
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eea1918b-3001-4205-a647-9dbbfa85f6e7 (old id 3590827)
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http://www.ncbi.nlm.nih.gov/pubmed/22875621
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2013-03-20 14:26:25
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@article{eea1918b-3001-4205-a647-9dbbfa85f6e7,
  abstract     = {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},
  author       = {Palumbo, Antonio and Waage, Anders and Hulin, Cyrille and Beksac, Meral and Zweegman, Sonja and Gay, Francesca and Gimsing, Peter and Leleu, Xavier and Wijermans, Pierre and Sucak, Gulsan and Pezzatti, Sara and Juliusson, Gunnar and Pegourie, Brigitte and Schaafsma, Martijn and Galli, Monica and Turesson, Ingemar and Kolb, Brigitte and van der Holt, Bronno and Baldi, Ileana and Rolke, Jurgen and Ciccone, Giovannino and Wetterwald, Marc and Lokhorst, Henk and Boccadoro, Mario and Rodon, Philippe and Sonneveld, Pieter},
  issn         = {1592-8721},
  language     = {eng},
  number       = {1},
  pages        = {87--94},
  publisher    = {Ferrata Storti Foundation},
  series       = {Haematologica},
  title        = {Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials},
  url          = {http://dx.doi.org/10.3324/haematol.2012.067058},
  volume       = {98},
  year         = {2013},
}