Original Article

Leukemia (2013) 27, 2056–2061; doi:10.1038/leu.2013.166; published online 25 June 2013

Corrected online: 9 October 2013

There is a Corrigendum (1 October 2013) associated with this article.


A multiparameter flow cytometry immunophenotypic algorithm for the identification of newly diagnosed symptomatic myeloma with an MGUS-like signature and long-term disease control

B Paiva1,2, M-B Vídriales1,2, L Rosiñol3, J Martínez-López4, M-V Mateos1,2, E M Ocio1,2, M-Á Montalbán4, L Cordón5, N C Gutiérrez1,2, L Corchete1,2, A Oriol6, M-J Terol7, M-A Echeveste8, R De Paz9, F De Arriba10, L Palomera11, J de la Rubia5, J Díaz-Mediavilla12, M Granell13, A Gorosquieta14, A Alegre15, A Orfao2,16, J-J Lahuerta4, J Bladé3 and J F San Miguel1,2 on behalf of the GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group

  1. 1Hospital Universitario de Salamanca, Salamanca, Spain
  2. 2IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain
  3. 3Hospital Clínic, IDIBAPS, Barcelona, Spain
  4. 4Hospital 12 de Octubre, Madrid, Spain
  5. 5Hospital Universitario de la Fe, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain
  6. 6Hospital Universitari Germans Trias i Pujol, Badalona, Spain
  7. 7Hospital Clínico de Valencia, Valencia, Spain
  8. 8Hospital de Donostia, San Sebastian, Spain
  9. 9Hospital Universitario La Paz, Madrid, Spain
  10. 10Hospital Morales Meseguer, Murcia, Spain
  11. 11Hospital Lozano Blesa, Zaragoza, Spain
  12. 12Hospital Clínico San Carlos, Madrid, Spain
  13. 13Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  14. 14Hospital Universitario Navarra, Pamplona, Spain
  15. 15Hospital Universitario La Princesa, Madrid, Spain
  16. 16Servicio General de Citometría and Department of Medicine, Universidad de Salamanca, Salamanca, Spain

Correspondence: Professor JFS Miguel, Hospital Universitario de Salamanca, Paseo de San Vicente 58–182 37007 Salamanca, Spain. E-mail: sanmigiz@usal.es

Received 7 May 2013; Revised 27 May 2013; Accepted 30 May 2013
Accepted article preview online 7 June 2013; Advance online publication 25 June 2013



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.

This article has been corrected since Advance Online Publication and a corrigendum is also printed in this issue


myeloma; plasma cells; flow cytometry; immunophenotyping; survival; Euroflow