Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation

Abstract

Minimal residual disease (MRD) assessment is standard in many hematologic malignancies but is considered investigational in multiple myeloma (MM). We report a prospective analysis of the prognostic importance of MRD detection by multiparameter flow cytometry (MFC) in 295 newly diagnosed MM patients uniformly treated in the GEM2000 protocol VBMCP/VBAD induction plus autologous stem cell transplantation [ASCT]). MRD status by MFC was determined at day 100 after ASCT. Progression-free survival (PFS; median 71 vs 37 months, P < .001) and overall survival (OS; median not reached vs 89 months, P = .002) were longer in patients who were MRD negative versus MRD positive at day 100 after ASCT. Similar prognostic differentiation was seen in 147 patients who achieved immunofixation-negative complete response after ASCT. Moreover, MRD(-) immunofixation-negative (IFx(-)) patients and MRD(-) IFx(+) patients had significantly longer PFS than MRD(+) IFx(-) patients. Multivariate analysis identified MRD status by MFC at day 100 after ASCT as the most important independent prognostic factor for PFS (HR = 3.64, P = .002) and OS (HR = 2.02, P = .02). Our findings demonstrate the clinical importance of MRD evaluation by MFC, and illustrate the need for further refinement of MM re-sponse criteria. This trial is registered at http://clinicaltrials.gov under identifier NCT00560053.

Figure 1

Progression-free survival and overall survival according to the presence or absence of MM-PCs in the bone marrow at day 100 after ASCT. (A,B) Progression-free survival (PFS) and overall survival (OS) for all patients included in the present analysis (N = 295). (C,D) PFS and OS among the subset of patients achieving CR (n = 147).

Figure 2

Prognostic influence of MRD status by MFC and IFX status at day 100 after ASCT. Progression-free survival (A) and overall survival (B) among specific risk groups of patients.

Figure 3

Prognostic influence of sequential MRD status by MFC before and after ASCT. (A) PFS and (B) OS (n = 157).