Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a GEM/PETHEMA study

Br J Haematol. 2013 Dec;163(5):581-9. doi: 10.1111/bjh.12576. Epub 2013 Oct 3.

Abstract

Minimal residual disease monitoring is becoming increasingly important in multiple myeloma (MM), but multiparameter flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques are not routinely available. This study investigated the prognostic influence of achieving molecular response assessed by fluorescent-PCR (F-PCR) in 130 newly diagnosed MM patients from Grupo Español Multidisciplinar de Melanoma (GEM)2000/GEM05 trials (NCT00560053, NCT00443235, NCT00464217) who achieved almost very good partial response after induction therapy. As a reference, we used the results observed with simultaneous MFC. F-PCR at diagnosis was performed on DNA using three different multiplex PCRs: IGH D-J, IGK V-J and KDE rearrangements. The applicability of F-PCR was 91·5%. After induction therapy, 64 patients achieved molecular response and 66 non-molecular response; median progression-free survival (PFS) was 61 versus 36 months, respectively (P = 0·001). Median overall survival (OS) was not reached (NR) in molecular response patients (5-year survival: 75%) versus 66 months in the non-molecular response group (P = 0·03). The corresponding PFS and OS values for patients with immunophenotypic versus non-immunophenotypic response were 67 versus 42 months (P = 0·005) and NR (5-year survival: 95%) versus 69 months (P = 0·004), respectively. F-PCR analysis is a rapid, affordable, and easily performable technique that, in some circumstances, may be a valid approach for minimal residual disease investigations in MM.

Keywords: IGH; Multiple myeloma; flow cytometry; fluorescent-PCR; minimal residual disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clinical Trials, Phase III as Topic / statistics & numerical data
  • DNA, Neoplasm / genetics
  • Diagnostic Tests, Routine / economics
  • Female
  • Flow Cytometry / economics
  • Fluorometry / economics
  • Fluorometry / methods
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain*
  • Gene Rearrangement, B-Lymphocyte, Light Chain*
  • Genes, Immunoglobulin*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Multicenter Studies as Topic / statistics & numerical data
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Multiple Myeloma / surgery
  • Neoplasm, Residual
  • Polymerase Chain Reaction / economics
  • Polymerase Chain Reaction / methods*
  • Prognosis
  • Sensitivity and Specificity
  • Transplantation, Autologous

Substances

  • DNA, Neoplasm

Associated data

  • ClinicalTrials.gov/NCT00443235
  • ClinicalTrials.gov/NCT00464217
  • ClinicalTrials.gov/NCT00560053