Bortezomib-containing induction regimens in transplant-eligible myeloma patients: a meta-analysis of phase 3 randomized clinical trials

Cancer. 2013 Dec 1;119(23):4119-28. doi: 10.1002/cncr.28325. Epub 2013 Sep 4.

Abstract

Background: The objective of this meta-analysis in patients with myeloma was to test the hypothesis that the addition of bortezomib to induction therapy not only improves the depth of response but also improves post-transplant progression-free survival (PFS) and overall survival (OS) outcomes.

Methods: Phase 3 trials that randomized newly diagnosed, transplant-eligible patients with myeloma to receive either a bortezomib-containing induction regimen (BCIR) or a nonbortezomib-containing induction regimen (NBCIR) were identified. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adapted for data synthesis, and comprehensive meta-analysis software was used to report pooled data as hazard ratios or odds ratios under a random-effects model.

Results: Four published phase 3 trials that included 2169 patients were analyzed. The postinduction and post-transplant pooled odds ratio for achieving a complete response/near complete response or a very good partial response or better and the overall response rate were higher with BCIR. The pooled hazard ratios for 3-year PFS and OS were 0.71 (95% confidence interval, 0.60-0.83; P < .00,001) and 0.79 (95% confidence interval, 0.66-0.96; P = .014), respectively, favoring BCIR. The odds of developing selected grade ≥ 3 toxicities (peripheral neuropathy and varicella-zoster virus reactivation) also were higher with BCIR.

Conclusions: The current meta-analysis demonstrated that BCIR results in an improved depth of response, which translates into improved post-transplant PFS and OS outcomes despite a higher incidence of toxicity. This analysis supports the concept that the choice of induction regimen can influence post-transplant outcomes such as PFS and OS.

Keywords: bortezomib-containing induction regimen; induction therapy; multiple myeloma; nonbortezomib-containing induction regimen; transplant-eligible.

Publication types

  • Clinical Trial, Phase III
  • Meta-Analysis
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Boronic Acids / administration & dosage*
  • Boronic Acids / adverse effects
  • Bortezomib
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy
  • Pyrazines / administration & dosage*
  • Pyrazines / adverse effects
  • Stem Cell Transplantation*
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Boronic Acids
  • Pyrazines
  • Bortezomib