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

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.

• Authors: Joaquin Martinez-Lopez, Elena Fernández-Redondo, Ramón García-Sánz, María Angeles Montalbán, Pilar Martínez-Sánchez, Bruno Pavia, María Victoria Mateos, Laura Rosiñol, Marisa Martín, Rosa Ayala, Rafael Martínez, María Jesus Blanchard, Adrian Alegre, Joan Besalduch, Joan Bargay, Miguel T Hernandez, María Eugenia Sarasquete, Pedro Sanchez-Godoy, Manuela Fernández, Joan Blade, Jesús F San Miguel, Juan Jose Lahuerta, GEM (Grupo Español Multidisciplinar de Melanoma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group
• Journal: British journal of haematology (Br J Haematol) Vol. 163 Issue 5 Pg. 581-9 (Dec 2013) ISSN: 1365-2141 [Electronic] England
• PMID: 24117042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons Ltd.

Chemical References

• DNA, Neoplasm

Topics

• 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, 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, genetics, mortality, pathology, surgery)
• Neoplasm, Residual
• Polymerase Chain Reaction (economics, methods)
• Prognosis
• Sensitivity and Specificity
• Transplantation, Autologous