Characterization of haematological parameters with bortezomib-melphalan-prednisone versus melphalan-prednisone in newly diagnosed myeloma, with evaluation of long-term outcomes and risk of thromboembolic events with use of erythropoiesis-stimulating agents: analysis of the VISTA trial

Br J Haematol. 2011 Apr;153(2):212-21. doi: 10.1111/j.1365-2141.2011.08569.x. Epub 2011 Mar 6.

Abstract

Although haematological toxicities, such as anaemia, are common in multiple myeloma (MM), no clear consensus exists on the use and impact of erythropoiesis-stimulating agents (ESA) on outcomes in MM. This analysis characterizes haematological toxicities and associated interventions in the phase III VISTA (Velcade(®) as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone) study of bortezomib plus melphalan/prednisone (VMP, n = 344) versus MP (n = 338) in previously untreated MM patients ineligible for high-dose therapy, and evaluates the impact of ESA use or red-blood-cell (RBC) transfusions on outcomes and thromboembolic risk. Incidence of haematological toxicities was similar with VMP and MP; similar rates of interventions and associated complications (e.g. bleeding, febrile neutropenia) were observed. Two hundred thirty three patients received ESA; 204 had RBC transfusions. Frequency of thromboembolic events was low and not affected by ESA use. Median time-to progression (TTP) was similar between ESA/non-ESA [hazard ratio: 1·03 (95% confidence interval 0·76-1·39); P = 0·8478] in both arms (VMP: 19·9/not reached; MP: 15·0/17·5 months). Three-year overall survival (OS) rates were similar between ESA/non-ESA in each arm. Patients receiving RBC transfusions had significantly shorter OS (P < 0·0001) versus non-RBC-transfusion patients. In conclusion, bortezomib did not add to melphalan haematological toxicity. Concomitant ESA use with VMP/MP in previously untreated MM patients did not adversely affect TTP or OS, or increase thromboembolic risk. However, RBC transfusion was associated with significantly shorter survival.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Boronic Acids / administration & dosage
  • Boronic Acids / adverse effects
  • Bortezomib
  • Disease-Free Survival
  • Erythrocyte Transfusion*
  • Female
  • Hematinics* / administration & dosage
  • Hematinics* / adverse effects
  • Humans
  • Incidence
  • Male
  • Melphalan / administration & dosage
  • Melphalan / adverse effects
  • Middle Aged
  • Multiple Myeloma* / mortality
  • Multiple Myeloma* / therapy
  • Prednisolone / administration & dosage
  • Prednisolone / adverse effects
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Survival Rate
  • Thromboembolism* / etiology
  • Thromboembolism* / mortality
  • Thromboembolism* / therapy

Substances

  • Boronic Acids
  • Hematinics
  • Pyrazines
  • Bortezomib
  • Prednisolone
  • Melphalan