Outcomes with two different schedules of bortezomib, melphalan, and prednisone (VMP) for previously untreated multiple myeloma: matched pair analysis using long-term follow-up data from the phase 3 VISTA and PETHEMA/GEM05 trials

Ann Hematol. 2016 Dec;95(12):2033-2041. doi: 10.1007/s00277-016-2835-3. Epub 2016 Oct 14.

Abstract

Bortezomib-melphalan-prednisone (VMP) is a standard-of-care for previously untreated, transplant-ineligible multiple myeloma (MM). Here, we compared outcomes between VMP regimens in the VISTA trial (9-cycle VMP schedule, including 4 cycles of twice weekly bortezomib) and the PETHEMA/GEM05 trial (less intensive 6-cycle VMP schedule with 1 cycle of twice weekly and 5 cycles of weekly bortezomib, then bortezomib-based maintenance). A total of 113 patient pairs matched by propensity score (estimated using logistic regression and incorporating eight exposure/outcome-related parameters) were included in this retrospective analysis. Median cumulative bortezomib dose was higher in PETHEMA/GEM05 than VISTA (49.6 vs 37.0 mg/m2); median dose intensity was lower (2.0 vs 5.1 mg/m2/month). Median progression-free survival (PFS) and time-to-progression (TTP) were significantly longer in PETHEMA/GEM05 than VISTA (PFS, 30.5 vs 20.0 months, p = 0.0265; TTP, 33.8 vs 24.2 months, p = 0.0049) after a median follow-up of 77.2 and 26.0 months, respectively. Median overall survival (OS) was similar (61.3 vs 61.0 months, p = 0.6528; median follow-up, 77.6 vs 60.1 months). Post-induction complete response rate was lower in PETHEMA/GEM05 than VISTA (19 vs 31 %; p = 0.03318); on-study (including maintenance) rate was similar (30 vs 31 %; p = 0.89437). This analysis suggests that the less-intensive PETHEMA/GEM05 VMP regimen plus maintenance may improve PFS and TTP, but not OS, compared with the VISTA VMP regimen.

Trial registrations: NCT00111319, NCT00443235.

Keywords: Bortezomib; Melphalan; Multiple myeloma; PETHEMA/GEM05; Prednisone; VISTA.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Bortezomib / administration & dosage*
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Matched-Pair Analysis
  • Melphalan / administration & dosage*
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / drug therapy*
  • Prednisone / administration & dosage*
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Bortezomib
  • Melphalan
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT00111319
  • ClinicalTrials.gov/NCT00443235