Longitudinal minimal residual disease assessment in multiple myeloma patients in complete remission – results from the NMSG flow-MRD substudy within the EMN02/HO95 MM trial

BMC Cancer

Rasmus Froberg Brøndum¹  Julie Støve Bødker¹  Alexander Schmitz¹  Martin Bøgsted²  Karen Dybkær²  Hans Erik Johnsen³  Marianne T. Severinsen⁴  Anne Stidsholt Roug⁴  Henrik Gregersen⁵  Vincent van der Velden⁶  Davine Hofste op Bruinink⁶  Pieter Sonneveld⁷  Bronno van der Holt⁸  Niels Frost Andersen⁹  Niels Abildgaard^1,10  Ulf Christian Frølund^1,11  Einar Haukas^1,12  Peter Gimsing^1,13  Carsten Helleberg^1,14  Lucia Ahlberg^1,15  Bjorn Andreasson^1,16  Anders Waage^1,17  Nina Gulbrandsen^1,18  Fredrik H. Schjesvold^1,18  Markus Hansson^1,19  Ulf-Henrik Mellqvist^2,20  Birgitta Lauri^2,21 

[1] Department of Haematology, Aalborg University Hospital, Forskningens Hus, Søndre Skovvej 15, DK-9000, Aalborg, Denmark;Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark;Department of Haematology, Aalborg University Hospital, Forskningens Hus, Søndre Skovvej 15, DK-9000, Aalborg, Denmark;Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark;Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;Department of Haematology, Aalborg University Hospital, Forskningens Hus, Søndre Skovvej 15, DK-9000, Aalborg, Denmark;Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark;Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;For the Nordic Myeloma Study Group (NMSG);Department of Haematology, Aalborg University Hospital, Forskningens Hus, Søndre Skovvej 15, DK-9000, Aalborg, Denmark;Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;Department of Haematology, Aalborg University Hospital, Forskningens Hus, Søndre Skovvej 15, DK-9000, Aalborg, Denmark;Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;For the Nordic Myeloma Study Group (NMSG);Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands;Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands;For the European Myeloma Network (EMN);Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands;HOVON Data Center, Department of Haematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands;For the Nordic Myeloma Study Group (NMSG);Department of Haematology, Aarhus University Hospital, Aarhus, Denmark;For the Nordic Myeloma Study Group (NMSG);Department of Haematology, Odense University Hospital, Odense, Denmark;For the Nordic Myeloma Study Group (NMSG);Department of Haematology, Sjællands Universitetshospital, Roskilde, Denmark;For the Nordic Myeloma Study Group (NMSG);Department of Haematology, Stavanger University Hospital, Stavanger, Norway;For the Nordic Myeloma Study Group (NMSG);Department of Haematology, University of Copenhagen, Copenhagen, Denmark;For the Nordic Myeloma Study Group (NMSG);Department of Hematology, Herlev Hospital, Herlev, Denmark;For the Nordic Myeloma Study Group (NMSG);Division of Hematology, Linkoping University Hospital, Linkoping, Sweden;For the Nordic Myeloma Study Group (NMSG);NU Hospital Group, Uddevalla hospital, Uddevalla, Sweden;For the Nordic Myeloma Study Group (NMSG);Norwegian University of Science and Technology and St. Olav’s University Hospital, Trondheim, Norway;For the Nordic Myeloma Study Group (NMSG);Oslo Myeloma Center, Department of Haematology, Oslo University Hospital, Olso, Norway;KG Jebsen Center for B Cell Malignancies, University of Oslo, Oslo, Norway;For the Nordic Myeloma Study Group (NMSG);Skane University Hospital, Lund, Sweden;For the Nordic Myeloma Study Group (NMSG);South Elvsborg Hospital, Boras, Sweden;For the Nordic Myeloma Study Group (NMSG);Sunderby Hospital, Luleaa, Sweden;

关键词: Multiple myeloma;    Minimal residual disease;    Flow cytometry;   

DOI  :  10.1186/s12885-022-09184-1

来源: Springer

【 摘 要 】

BackgroundMultiple myeloma remains an incurable disease with multiple relapses due to residual myeloma cells in the bone marrow of patients after therapy. Presence of small number of cancer cells in the body after cancer treatment, called minimal residual disease, has been shown to be prognostic for progression-free and overall survival. However, for multiple myeloma, it is unclear whether patients attaining minimal residual disease negativity may be candidates for treatment discontinuation. We investigated, if longitudinal flow cytometry-based monitoring of minimal residual disease (flow-MRD) may predict disease progression earlier and with higher sensitivity compared to biochemical assessments.MethodsPatients from the Nordic countries with newly diagnosed multiple myeloma enrolled in the European-Myeloma-Network-02/Hovon-95 (EMN02/HO95) trial and undergoing bone marrow aspiration confirmation of complete response, were eligible for this Nordic Myeloma Study Group (NMSG) substudy. Longitdudinal flow-MRD assessment of bone marrow samples was performed to identify and enumerate residual malignant plasma cells until observed clinical progression.ResultsMinimal residual disease dynamics were compared to biochemically assessed changes in serum free light chain and M-component. Among 20 patients, reaching complete response or stringent complete response during the observation period, and with ≥3 sequential flow-MRD assessments analysed over time, increasing levels of minimal residual disease in the bone marrow were observed in six cases, preceding biochemically assessed disease and clinical progression by 5.5 months and 12.6 months (mean values), respectively. Mean malignant plasma cells doubling time for the six patients was 1.8 months (95% CI, 1.4–2.3 months). Minimal malignant plasma cells detection limit was 4 × 10–5.ConclusionsFlow-MRD is a sensitive method for longitudinal monitoring of minimal residual disease dynamics in multiple myeloma patients in complete response. Increasing minimal residual disease levels precedes biochemically assessed changes and is an early indicator of subsequent clinical progression.Trial registrationNCT01208766

【 授权许可】

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