title: 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.
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.forename: Maria-Belén
authors.initials: MB
authors.lastname: Vidriales
authors.forename: Jorge
authors.initials: J
authors.lastname: Cerveró
authors.forename: Gema
authors.initials: G
authors.lastname: Mateo
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Pérez
authors.forename: Maria A
authors.initials: MA
authors.lastname: Montalbán
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Laura
authors.initials: L
authors.lastname: Montejano
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: Alfonso
authors.initials: A
authors.lastname: García de Coca
authors.forename: Natalia
authors.initials: N
authors.lastname: de Las Heras
authors.forename: Maria V
authors.initials: MV
authors.lastname: Mateos
authors.forename: Maria C
authors.initials: MC
authors.lastname: López-Berges
authors.forename: Raimundo
authors.initials: R
authors.lastname: García-Boyero
authors.forename: Josefina
authors.initials: J
authors.lastname: Galende
authors.forename: Jose
authors.initials: J
authors.lastname: Hernández
authors.forename: Luis
authors.initials: L
authors.lastname: Palomera
authors.forename: Dolores
authors.initials: D
authors.lastname: Carrera
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martín
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001761:Bleomycin / Q000008:administration & dosage; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D018365:Neoplasm, Residual; D011237:Predictive Value of Tests; D033581:Stem Cell Transplantation / Q000379:methods; D015996:Survival Rate; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D001761:Bleomycin; D016685:Mitomycin; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D002945:Cisplatin; D002330:Carmustine