title: 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.affiliation: Servicio de Hematología & Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martinez-Lopez
authors.forename: Elena
authors.initials: E
authors.lastname: Fernández-Redondo
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sánz
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Montalbán
authors.forename: Pilar
authors.initials: P
authors.lastname: Martínez-Sánchez
authors.forename: Bruno
authors.initials: B
authors.lastname: Pavia
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: Marisa
authors.initials: M
authors.lastname: Martín
authors.forename: Rosa
authors.initials: R
authors.lastname: Ayala
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez
authors.forename: María Jesus
authors.initials: MJ
authors.lastname: Blanchard
authors.forename: Adrian
authors.initials: A
authors.lastname: Alegre
authors.forename: Joan
authors.initials: J
authors.lastname: Besalduch
authors.forename: Joan
authors.initials: J
authors.lastname: Bargay
authors.forename: Miguel T
authors.initials: MT
authors.lastname: Hernandez
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Sarasquete
authors.forename: Pedro
authors.initials: P
authors.lastname: Sanchez-Godoy
authors.forename: Manuela
authors.initials: M
authors.lastname: Fernández
authors.forename: Joan
authors.initials: J
authors.lastname: Blade
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Lahuerta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D004273:DNA, Neoplasm / Q000235:genetics; D003955:Diagnostic Tests, Routine / Q000191:economics; D005260:Female; D005434:Flow Cytometry / Q000191:economics; D005470:Fluorometry / Q000191:economics / Q000379:methods; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction / Q000191:economics / Q000379:methods*; D011379:Prognosis; D012680:Sensitivity and Specificity; D014182:Transplantation, Autologous
chemical_list: D004273:DNA, Neoplasm
keywords: IGH; Multiple myeloma; flow cytometry; fluorescent-PCR; minimal residual disease