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Article

Comparison of NGS and MFC Methods: Key Metrics in Multiple Myeloma MRD Assessment

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Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany
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National Center for Tumor Diseases Heidelberg, 69120 Heidelberg, Germany
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Department of Hematology, Oncology and Immunology, University Hospital Tübingen, 72076 Tübingen, Germany
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Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, 40225 Düsseldorf, Germany
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Department of Internal Medicine III, Klinikum Chemnitz, 09113 Chemnitz, Germany
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Department of Internal Medicine III, University Medical Center Mainz, 55131 Mainz, Germany
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Department of Oncology, Hematology and Bone Marrow Transplantation with Department of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
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Medical Clinic, Charité University Medicine Berlin, 10117 Berlin, Germany
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Department of Hematology, Oncology and Immunology, Philipps-University Marburg, 35043 Marburg, Germany
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Authors to whom correspondence should be addressed.
German-speaking Myeloma Multicenter Group (GMMG), Germany, https://www.gmmg.info/.
Cancers 2020, 12(8), 2322; https://doi.org/10.3390/cancers12082322
Received: 13 July 2020 / Revised: 5 August 2020 / Accepted: 6 August 2020 / Published: 18 August 2020
(This article belongs to the Section Cancer Biomarkers)
In order to meet the challenges in data evaluation and comparability between studies in multiple myeloma (MM) minimal residual disease (MRD) assessment, the goal of the current study was to provide a step-by-step evaluation of next-generation sequencing (NGS) and multicolor flow cytometry (MFC) data. Bone marrow (BM) sample pairs from 125 MM patients were analyzed by NGS and MFC MM MRD methods. Tumor load (TL) and limit of detection (LOD) and quantification (LOQ) were calculated. The best-fit MRD cut-off was chosen as 1 × 10−5, resulting in an overall 9.6% (n overall = 12 (NGS n = 2, MFC n = 10)) nonassessable cases. The overall concordance rate between NGS and MFC was 68.0% (n = 85); discordant results were found in 22.4% (11.2% (n = 14) of cases in each direction. Overall, 55.1% (n = 60/109) and 49.5% (n = 54/109) of patients with a serological response ≥ very good partial response (VGPR) showed BM MRD negativity by NGS and MFC, respectively. A good correlation in the TL assessed by both techniques was found (correlation coefficient = 0.8, n = 40, p < 0.001). Overall, our study shows good concordance between MM BM MRD status and TL when comparing NGS and MFC at a threshold of 10–5. However, a sufficient number of analyzed events and calculation of MRD key metrics are essential for the comparison of methods and evaluability of data at a specific MRD cut-off. View Full-Text
Keywords: multiple myeloma (MM); minimal residual disease (MRD); next-generation sequencing (NGS); multicolor flow cytometry (MFC); EuroFlow multiple myeloma (MM); minimal residual disease (MRD); next-generation sequencing (NGS); multicolor flow cytometry (MFC); EuroFlow
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MDPI and ACS Style

Kriegsmann, K.; Hundemer, M.; Hofmeister-Mielke, N.; Reichert, P.; Manta, C.-P.; Awwad, M.H.S.; Sauer, S.; Bertsch, U.; Besemer, B.; Fenk, R.; Hänel, M.; Munder, M.; Weisel, K.C.; Blau, I.W.; Neubauer, A.; Müller-Tidow, C.; Raab, M.S.; Goldschmidt, H.; Huhn, S.; for the German-speaking Myeloma Multicenter Group. Comparison of NGS and MFC Methods: Key Metrics in Multiple Myeloma MRD Assessment. Cancers 2020, 12, 2322. https://doi.org/10.3390/cancers12082322

AMA Style

Kriegsmann K, Hundemer M, Hofmeister-Mielke N, Reichert P, Manta C-P, Awwad MHS, Sauer S, Bertsch U, Besemer B, Fenk R, Hänel M, Munder M, Weisel KC, Blau IW, Neubauer A, Müller-Tidow C, Raab MS, Goldschmidt H, Huhn S, for the German-speaking Myeloma Multicenter Group. Comparison of NGS and MFC Methods: Key Metrics in Multiple Myeloma MRD Assessment. Cancers. 2020; 12(8):2322. https://doi.org/10.3390/cancers12082322

Chicago/Turabian Style

Kriegsmann, Katharina, Michael Hundemer, Nicole Hofmeister-Mielke, Philipp Reichert, Calin-Petru Manta, Mohamed H.S. Awwad, Sandra Sauer, Uta Bertsch, Britta Besemer, Roland Fenk, Mathias Hänel, Markus Munder, Katja C. Weisel, Igor W. Blau, Andreas Neubauer, Carsten Müller-Tidow, Marc S. Raab, Hartmut Goldschmidt, Stefanie Huhn, and for the German-speaking Myeloma Multicenter Group. 2020. "Comparison of NGS and MFC Methods: Key Metrics in Multiple Myeloma MRD Assessment" Cancers 12, no. 8: 2322. https://doi.org/10.3390/cancers12082322

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