Overcoming the response plateau in multiple myeloma: a novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization. Academic Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Antigens, CD34
  • Antineoplastic Agents
  • Bortezomib
  • Cyclophosphamide
  • Drug Resistance, Neoplasm
  • Drug-Related Side Effects and Adverse Reactions
  • Filgrastim
  • Gene Expression Regulation, Neoplastic
  • Granulocyte Colony-Stimulating Factor
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Recombinant Proteins
  • Signal Transduction

MeSH Major

  • Boronic Acids
  • Dexamethasone
  • Multiple Myeloma
  • Neoplastic Stem Cells
  • Pyrazines

abstract

  • This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥ VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥ VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 10(6) cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥ 3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield.

publication date

  • March 15, 2013

has subject area

  • Adult
  • Aged
  • Antigens, CD34
  • Antineoplastic Agents
  • Boronic Acids
  • Bortezomib
  • Cyclophosphamide
  • Dexamethasone
  • Drug Resistance, Neoplasm
  • Drug-Related Side Effects and Adverse Reactions
  • Filgrastim
  • Gene Expression Regulation, Neoplastic
  • Granulocyte Colony-Stimulating Factor
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma
  • Neoplasm Staging
  • Neoplastic Stem Cells
  • Pyrazines
  • Recombinant Proteins
  • Signal Transduction

Research

keywords

  • Clinical Trial, Phase II
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4020015

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-12-1429

PubMed ID

  • 23357980

Additional Document Info

start page

  • 1534

end page

  • 1546

volume

  • 19

number

  • 6