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

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 VeldeJesús F. San Miguel

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

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 1.3mg/m 2, days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, days 1, 8, 22, 29, cycles 5-9, plus melphalan 9mg/m 2 and prednisone 60mg/m 2, 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 694.4pg/mL and increased with MP by 1273.3pg/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.

Original languageEnglish
Pages (from-to)372-384
Number of pages13
JournalEuropean Journal of Haematology
Volume86
Issue number5
DOIs
StatePublished - 1 May 2011
Externally publishedYes

Keywords

  • Bone
  • Bortezomib
  • Melphalan-prednisone
  • Myeloma
  • VISTA

ASJC Scopus subject areas

  • Hematology

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