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.

Author(s): Delforge M, Terpos E, Richardson PG, Shpilberg O, Khuageva NK, Schlag R, Dimopoulos MA, Kropff M, Spicka I, Petrucci MT, Samoilova OS, Mateos MV, Magen-Nativ H, Goldschmidt H, Esseltine DL, Ricci DS, Liu K, Deraedt W, Cakana A, van de Velde H, San Miguel JF

Affiliation(s): Myeloma Study Group, Belgian Hematological Society, Belgium. michel.delforge@uzleuven.be

Publication date & source: 2011-05, Eur J Haematol., 86(5):372-84. Epub 2011 Mar 30.

Publication type: Clinical Trial, Phase III; Multicenter Study; Randomized Controlled Trial

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/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. (c) 2011 John Wiley & Sons A/S.