title: A multiparameter flow cytometry immunophenotypic algorithm for the identification of newly diagnosed symptomatic myeloma with an MGUS-like signature and long-term disease control.
abstract: Achieving complete remission (CR) in multiple myeloma (MM) translates into extended survival, but two subgroups of patients fall outside this paradigm: cases with unsustained CR, and patients that do not achieve CR but return into a monoclonal gammopathy of undetermined significance (MGUS)-like status with long-term survival. Here, we describe a novel automated flow cytometric classification focused on the analysis of the plasma-cell compartment to identify among newly diagnosed symptomatic MM patients (N=698) cases with a baseline MGUS-like profile, by comparing them to MGUS (N=497) patients and validating the classification model in 114 smoldering MM patients. Overall, 59 symptomatic MM patients (8%) showed an MGUS-like profile. Despite achieving similar CR rates after high-dose therapy/autologous stem cell transplantation vs other MM patients, MGUS-like cases had unprecedented longer time-to-progression (TTP) and overall survival (OS; ~60% at 10 years; P<0.001). Importantly, MGUS-like MM patients failing to achieve CR showed similar TTP (P=0.81) and OS (P=0.24) vs cases attaining CR. This automated classification also identified MGUS patients with shorter TTP (P=0.001, hazard ratio: 5.53) and ultra-high-risk smoldering MM (median TTP, 15 months). In summary, we have developed a biomarker that identifies a subset of symptomatic MM patients with an occult MGUS-like signature and an excellent outcome, independently of the depth of response.
authors.affiliation: 1] Hospital Universitario de Salamanca, Salamanca, Spain [2] IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Paiva
authors.forename: M-B
authors.initials: MB
authors.lastname: Vídriales
authors.forename: L
authors.initials: L
authors.lastname: Rosiñol
authors.forename: J
authors.initials: J
authors.lastname: Martínez-López
authors.forename: M-V
authors.initials: MV
authors.lastname: Mateos
authors.forename: E M
authors.initials: EM
authors.lastname: Ocio
authors.forename: M-Á
authors.initials: MÁ
authors.lastname: Montalbán
authors.forename: L
authors.initials: L
authors.lastname: Cordón
authors.forename: N C
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: L
authors.initials: L
authors.lastname: Corchete
authors.forename: A
authors.initials: A
authors.lastname: Oriol
authors.forename: M-J
authors.initials: MJ
authors.lastname: Terol
authors.forename: M-A
authors.initials: MA
authors.lastname: Echeveste
authors.forename: R
authors.initials: R
authors.lastname: De Paz
authors.forename: F
authors.initials: F
authors.lastname: De Arriba
authors.forename: L
authors.initials: L
authors.lastname: Palomera
authors.forename: J
authors.initials: J
authors.lastname: de la Rubia
authors.forename: J
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.forename: M
authors.initials: M
authors.lastname: Granell
authors.forename: A
authors.initials: A
authors.lastname: Gorosquieta
authors.forename: A
authors.initials: A
authors.lastname: Alegre
authors.forename: A
authors.initials: A
authors.lastname: Orfao
authors.forename: J-J
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: J
authors.initials: J
authors.lastname: Bladé
authors.forename: J F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy; D010265:Paraproteinemias / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy; D010950:Plasma Cells / Q000473:pathology*; D011379:Prognosis; D012074:Remission Induction; D014182:Transplantation, Autologous