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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., (© 2013 John Wiley & Sons Ltd.)

This study aimed to standardize a simple molecular method for evaluating the response to treatment in multiple myeloma (MM) patients after high dose chemotherapy. Fifty three patients enrolled in the GEM2000 protocol were studied for minimal residual disease (MRD) using both fluorescent-polymerase chain reaction (F-PCR) and flow cytometry. Most patients had achieved complete remission or very good response after autologous stem cell transplantation. The molecular analysis of immunoglobulin gene rearrangements at diagnosis and during the follow-up was carried out by F-PCR according to the Biomed-2 protocols. F-PCR could be used in 91% of the patients and the results were similar to flow cytometry. F-PCR was able to identify a group of patients with a better prognosis [progression-free survival (PFS) 67.86% in patients with negative F-PCR vs. 28%; P = 0.001], even amongst patients who achieved a complete response with negative immunofixation (PFS 75% vs. 25%; P = 0.002). Multivariate analysis identified the F-PCR result as the only variable to show a prognostic value when PFS was analysed. F-PCR of DHJ and light chain rearrangements of immunoglobulin genes is a feasible method for evaluating MRD in MM patients after intensive therapy. Achieving molecular response by F-PCR shows prognostic value.

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. [ABSTRACT FROM AUTHOR]