Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study

Blood. 2012 Aug 23;120(8):1589-96. doi: 10.1182/blood-2012-02-408922. Epub 2012 Jul 12.

Abstract

The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone (VTD) versus thalidomide/dexamethasone (TD) versus vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib (VBMCP/VBAD/B) in patients aged 65 years or younger with multiple myeloma. The primary endpoint was complete response (CR) rate postinduction and post-autologous stem cell transplantation (ASCT). Three hundred eighty-six patients were allocated to VTD (130), TD (127), or VBMCP/VBAD/B (129). The CR rate was significantly higher with VTD than with TD (35% vs 14%, P = .001) or with VBMCP/VBAD/B (35% vs 21%, P = .01). The median progression-free survival (PFS) was significantly longer with VTD (56.2 vs 28.2 vs 35.5 months, P = .01). In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P = .004) or with VBMCP/VBAD/B (46% vs 38%, P = .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.gov (NCT00461747) and Eudra CT (no. 2005-001110-41).

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents / toxicity
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Boronic Acids / administration & dosage
  • Boronic Acids / adverse effects
  • Boronic Acids / therapeutic use*
  • Boronic Acids / toxicity
  • Bortezomib
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Dexamethasone / therapeutic use*
  • Dexamethasone / toxicity
  • Disease-Free Survival
  • Female
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Induction Chemotherapy
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy*
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Pyrazines / toxicity
  • Stem Cells / drug effects
  • Stem Cells / pathology
  • Thalidomide / administration & dosage
  • Thalidomide / adverse effects
  • Thalidomide / therapeutic use*
  • Thalidomide / toxicity
  • Transplantation, Autologous

Substances

  • Antineoplastic Agents
  • Boronic Acids
  • Pyrazines
  • Thalidomide
  • Bortezomib
  • Dexamethasone

Associated data

  • ClinicalTrials.gov/NCT00461747