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Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. melphalan-prednisone in the phase III VISTA trial in multiple myeloma

Objectives: Bone disease is a key presenting feature of myeloma. This post hoc analysis of the phase III VISTA trial of bortezomib plus melphalan-prednisone (VMP) vs. MP in previously untreated myeloma patients assessed clinical bone disease events and changes in alkaline phosphatase (ALP), a marker...

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Main Authors: Delforge, Michel (Author) , Terpos, Evangelos (Author) , Richardson, Paul G. (Author) , Shpilberg, Ofer (Author) , Khuageva, Nuriet K. (Author) , Schlag, Rudolf (Author) , Dimopoulos, Meletios A. (Author) , Kropff, Martin (Author) , Spicka, Ivan (Author) , Petrucci, Maria T. (Author) , Samoilova, Olga S. (Author) , Mateos, Maria-Victoria (Author) , Magen-Nativ, Hila (Author) , Goldschmidt, Hartmut (Author) , Esseltine, Dixie-Lee (Author) , Ricci, Deborah S. (Author) , Liu, Kevin (Author) , Deraedt, William (Author) , Cakana, Andrew (Author) , van de Velde, Helgi (Author) , San Miguel, Jesús F. (Author)
Format: Article (Journal)
Language:English
Published: 2011
In: European journal of haematology
Year: 2011, Volume: 86, Issue: 5, Pages: 372-384
ISSN:1600-0609
DOI:10.1111/j.1600-0609.2011.01599.x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.1600-0609.2011.01599.x
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0609.2011.01599.x
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Author Notes:Michel Delforge, Evangelos Terpos, Paul G. Richardson, Ofer Shpilberg, Nuriet K. Khuageva, Rudolf Schlag, Meletios A. Dimopoulos, Martin Kropff, Ivan Spicka, Maria T. Petrucci, Olga S. Samoilova, Maria-Victoria Mateos, Hila Magen-Nativ, Hartmut Goldschmidt, Dixie-Lee Esseltine, Deborah S. Ricci, Kevin Liu, William Deraedt, Andrew Cakana, Helgi van de Velde, Jesús F. San Miguel
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Summary:Objectives: Bone disease is a key presenting feature of myeloma. This post hoc analysis of the phase III VISTA trial of bortezomib plus melphalan-prednisone (VMP) vs. MP in previously untreated myeloma patients assessed clinical bone disease events and changes in alkaline phosphatase (ALP), a marker for osteoblast activation, and serum Dickkopf-1 (DKK-1), an inhibitor of osteoblast differentiation, during treatment. Methods: Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m2, days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, days 1, 8, 22, 29, cycles 5-9, plus melphalan 9 mg/m2 and prednisone 60 mg/m2, days 1-4, cycles 1-9; N = 344) or MP alone (N = 338). Results: Rates of bisphosphonates use during treatment (73% vs. 82%), progression because of worsening bone disease (3% vs. 11%), and requirement for subsequent radiotherapy (3% vs. 8%) were lower with VMP vs. MP. Median maximum ALP increase was significantly higher with VMP vs. MP overall (49.7% vs. 30.3%, P = 0.029), and higher by response group (complete response [CR]: 68.7% vs. 43.9%; partial response [PR]: 41.5% vs. 31.2%). Greater maximum ALP increase was strongly associated with achievement of CR (P ≤ 0.0001) and CR/PR (P ≤ 0.01). Median DKK-1 decreased with VMP by 694.4 pg/mL and increased with MP by 1273.3 pg/mL from baseline to day 4 (P = 0.0069). Available radiologic data revealed evidence of bone healing in 6/11 VMP-treated patients, who achieved best responses of three CR, one PR, and two stable disease. Conclusions: These results suggest a positive effect of bortezomib on bone metabolism and potentially bone healing in myeloma.
Item Description:Gesehen am 04.05.2022
Physical Description:Online Resource
ISSN:1600-0609
DOI:10.1111/j.1600-0609.2011.01599.x

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