title: Bortezomib-containing induction regimens in transplant-eligible myeloma patients: a meta-analysis of phase 3 randomized clinical trials.
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.
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Nooka
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Kaufman
authors.forename: Madhusmita
authors.initials: M
authors.lastname: Behera
authors.forename: Amelia
authors.initials: A
authors.lastname: Langston
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
authors.forename: Charise
authors.initials: C
authors.lastname: Gleason
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Boise
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D033581:Stem Cell Transplantation; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib
keywords: bortezomib-containing induction regimen; induction therapy; multiple myeloma; nonbortezomib-containing induction regimen; transplant-eligible