Autores: Delforge, M.; Terpos, E.; Richardson, P. G.; Shpilberg, O.; Khuageva, N. K.; Schlag, R.; Dimopoulos, M. A.; Kropff, M.; Spicka, I.; Petrucci, M. T.; Samoilova, O. S.; Mateos, M. V.; Magen-Nativ, H.; Goldschmidt, H.; Esseltine, D. L.; Ricci, D. S.; Liu, K.; Deraedt, W.; Cakana, A.; van de Velde, H.;
San Miguel Izquierdo, Jesús
Resumen:
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.
