Scientific publications

Next generation flow (NGF) for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

Flores-Montero J (1), Flores LS (1), Paiva B (2), Puig N (3), García-Sánchez O (3), Böttcher S (4), van der Velden VH (5), Pérez-Morán JJ (3), Vidriales MB (3), García-Sanz R (3), Jimenez C (3), González M (3), Martinez-López J (6), Mateos AC (1), Grigore GE (7), Fluxá R (7), Pontes R (8), Caetano J (9), Sedek L (10), Del Cañizo MC (3), Bladé J (11), Lahuerta JJ (6), Aguilar C (12), Bárez A (13), García-Mateo A (14), Labrador J (15), Leoz P (1), Aguilera-Sanz C (16), San-Miguel J (2), Mateos MV (3), Durie B (17), van Dongen JJ (5,18), Orfao A (1).
(1) Cancer Research Center (IBMCC-CSIC/USAL-IBSAL); General Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain (USAL).
(2) Clinica Universidad de Navarra; Applied Medical Research Center (CIMA), IDISNA, Pamplona, Spain (UNAV).
(3) Department of Hematology, University Hospital of Salamanca, IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain (HUSAL).
(4) Second Department of Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany (UNIKIEL).
(5) Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands (EMC).
(6) Department of Hematology, Madrid, Spain.
(7) Cytognos SL, Salamanca, Spain.
(8) Faculty of Medicine, Federal University of Rio de Janeiro and Institute of Pediatrics and Childhood Care Rio de Janeiro, Brazil.
(9) Department of Hematology, Portuguese Institute of Oncology, Lisbon, Portugal (IPOLFG).
(10) Department of Pediatric Hematology and Oncology, Medical University of Silesia in Katowice, Zabrze, Poland(SUM).
(11) Department of Hematology, Hospital Clinic I Provincial, Barcelona, Spain.
(12) Department of Hematology, Hospital General de Santa Bárbara, Soria, Spain.
(13) Department of Hematology, Complejo Asistencial de Ávila, Ávila, Spain.
(14) Department of Hematology, Complejo Asistencial de Segovia, Segovia, Spain.
(15) Hematology Department, Hospital Universitario de Burgos, Burgos, Spain.
(16) Department of Hematology, Hospital El Bierzo, Ponferrada, Spain.
(17) Cedars-Sinai Samuel Oschin Cancer Center, Los Angeles, CA, USA.
(18) Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. 

Magazine: Leukemia

Date: Jan 20, 2017

Haematology and Hameotherapy

ABSTRACT

Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy.

However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly-sensitive and standardized MRD detection in MM.

An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. Additionally, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating.

Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% PFS not reached vs 7 months; P=0.02).

This study establishes EuroFlow-based NGF as a highly-sensitive, fully-standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.

CITATION  Leukemia. 2017 Jan 20. doi: 10.1038/leu.2017.29

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