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Myeloma

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

Leukemia volume 27, pages 2056–2061 (2013)Cite this article

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A Corrigendum to this article was published on 09 October 2013

This article has been updated

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.

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  • 09 October 2013

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

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Acknowledgements

This work was supported by the Cooperative Research Thematic Network (RTICC) grants RD12/0036/0071, RD12/0036/0058, RD12/0036/0046, RD12/0036/0036 and RD12/0036/0048, of the Red de Cancer (Cancer Network of Excellence), Instituto de Salud Carlos III, Spain, Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS: PI060339; 06/1354; 02/0905; 01/0089/01-02; PS09/01897/01370; G03/136), Consejería de Sanidad, Junta de Castilla y León, Valladolid, Spain (557/A/10) and Asociación Española Contra el Cáncer (AECC; GCB120981SAN), Spain.

Author contributions

JFSM, J-JL, JB and A Orfao conceived the idea, and together with M-VM and LR designed the study protocol; BP, M-BV, M-AM, and LC analyzed the flow cytometry data; NCG analyzed the FISH data; LR, JM-L, M-VM, EMO, AO, M-JT, M-AE, RdP, FdA, LP, JdlR, JD-M, MG, AG, AA, J-JL, JB and JFSM contributed with provision of study material or patients; BP and JFSM analyzed and interpreted the data; BP and LC performed the statistical analysis; and BP and JFSM wrote the manuscript. All authors reviewed and approved the manuscript.

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Authors and Affiliations

  1. Hospital Universitario de Salamanca, Salamanca, Spain

    B Paiva, M-B Vídriales, M-V Mateos, E M Ocio, N C Gutiérrez, L Corchete & J F San Miguel

  2. IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain

    B Paiva, M-B Vídriales, M-V Mateos, E M Ocio, N C Gutiérrez, L Corchete, A Orfao & J F San Miguel

  3. Hospital Clínic, IDIBAPS, Barcelona, Spain

    L Rosiñol & J Bladé

  4. Hospital 12 de Octubre, Madrid, Spain

    J Martínez-López, M-Á Montalbán & J-J Lahuerta

  5. Hospital Universitario de la Fe, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain

    L Cordón & J de la Rubia

  6. Hospital Universitari Germans Trias i Pujol, Badalona, Spain

    A Oriol

  7. Hospital Clínico de Valencia, Valencia, Spain

    M-J Terol

  8. Hospital de Donostia, San Sebastian, Spain

    M-A Echeveste

  9. Hospital Universitario La Paz, Madrid, Spain

    R De Paz

  10. Hospital Morales Meseguer, Murcia, Spain

    F De Arriba

  11. Hospital Lozano Blesa, Zaragoza, Spain

    L Palomera

  12. Hospital Clínico San Carlos, Madrid, Spain

    J Díaz-Mediavilla

  13. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    M Granell

  14. Hospital Universitario Navarra, Pamplona, Spain

    A Gorosquieta

  15. Hospital Universitario La Princesa, Madrid, Spain

    A Alegre

  16. Servicio General de Citometría and Department of Medicine, Universidad de Salamanca, Salamanca, Spain

    A Orfao

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  1. B Paiva
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on behalf of the GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group

Corresponding author

Correspondence to J F San Miguel.

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Competing interests

JM-L, EMO, A Oriol, FdA, LP, JdlR and J-JL have received honoraria from Celgene and Janssen. BP has received honoraria from Millennium, Janssen, Celgene and the Binding Site. M-VM has served on the speaker’s bureau for Millennium, Celgene and Janssen. LR has received honoraria and has served on the advisory board for Janssen and Celgene, JB has received honoraria and has served on the advisory board for Janssen and Celgene, as well as grant support from Celgene and Janssen. JFSM has served on the speaker’s bureau and on the advisory board for, and has received honoraria from, Millennium, Janssen and Celgene. All other authors declare no conflict of interest.

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Paiva, B., Vídriales, MB., Rosiñol, L. et al. A multiparameter flow cytometry immunophenotypic algorithm for the identification of newly diagnosed symptomatic myeloma with an MGUS-like signature and long-term disease control. Leukemia 27, 2056–2061 (2013). https://doi.org/10.1038/leu.2013.166

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