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

• Published in: British journal of haematology Vol. 163; no. 5; pp. 581 - 589
• Main Authors: Martinez‐Lopez, Joaquin, Fernández‐Redondo, Elena, García‐Sánz, Ramón, Montalbán, María Angeles, Martínez‐Sánchez, Pilar, Pavia, Bruno, Mateos, María Victoria, Rosiñol, Laura, Martín, Marisa, Ayala, Rosa, Martínez, Rafael, Blanchard, María Jesus, Alegre, Adrian, Besalduch, Joan, Bargay, Joan, Hernandez, Miguel T., Sarasquete, María Eugenia, Sanchez‐Godoy, Pedro, Fernández, Manuela, Blade, Joan, San Miguel, Jesús F., Lahuerta, Juan Jose
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.12.2013
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Clinical Trials, Phase III as Topic - statistics & numerical data; Diagnostic Tests, Routine - economics; DNA, Neoplasm - genetics; Female; flow cytometry; Flow Cytometry - economics; fluorescent‐PCR; Fluorometry - economics; Fluorometry - methods; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Gene Rearrangement, B-Lymphocyte, Light Chain; Genes, Immunoglobulin; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation; Humans; IGH; Immunophenotyping; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; minimal residual disease; Multicenter Studies as Topic - statistics & numerical data; Multiple myeloma; 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; Tumors; Immunopathology; Flow cytometry; Heavy peptide chain; Immunoglobulins; Prognosis; Hematology; Multiple myeloma; Minimal residual disease; Malignant hemopathy; IGH; Myeloma; Polymerase chain reaction; Cancerology; Immunoglobulinopathy; Gene; Lymphoproliferative syndrome; fluorescent-PCR; Genetics; Molecular biology; Cancer; flow cytometry; minimal residual disease
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.12576

Summary 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.