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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. [ABSTRACT FROM AUTHOR]