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

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DOI

  • Alexander Schmitz
  • Rasmus Froberg Brøndum, Aalborg Universitet
  • ,
  • Hans Erik Johnsen, Aalborg Universitet
  • ,
  • Ulf Henrik Mellqvist, For the Nordic Myeloma Study Group (NMSG), South Elvsborg Hospital
  • ,
  • Anders Waage, For the Nordic Myeloma Study Group (NMSG), Norwegian University of Science and Technology
  • ,
  • Peter Gimsing
  • Davine Hofste op Bruinink, Erasmus University Rotterdam
  • ,
  • Vincent van der Velden, Erasmus University Rotterdam
  • ,
  • Bronno van der Holt, Erasmus University Rotterdam
  • ,
  • Markus Hansson, For the Nordic Myeloma Study Group (NMSG), Lund University
  • ,
  • Niels Frost Andersen, For the Nordic Myeloma Study Group (NMSG)
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  • Ulf Christian Frølund, For the Nordic Myeloma Study Group (NMSG), Københavns Universitet
  • ,
  • Carsten Helleberg, For the Nordic Myeloma Study Group (NMSG), Københavns Universitet
  • ,
  • Fredrik H. Schjesvold, For the Nordic Myeloma Study Group (NMSG), University of Oslo
  • ,
  • Lucia Ahlberg, For the Nordic Myeloma Study Group (NMSG), Linköping University
  • ,
  • Nina Gulbrandsen, For the Nordic Myeloma Study Group (NMSG), University of Oslo
  • ,
  • Bjorn Andreasson, For the Nordic Myeloma Study Group (NMSG), Skaraborg Hospital
  • ,
  • Birgitta Lauri, For the Nordic Myeloma Study Group (NMSG), Sunderby Hospital
  • ,
  • Einar Haukas, For the Nordic Myeloma Study Group (NMSG), Stavanger University Hospital
  • ,
  • Julie Støve Bødker, Aalborg Universitet
  • ,
  • Anne Stidsholt Roug
  • Martin Bøgsted
  • Marianne T. Severinsen, Aalborg Universitet
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  • Henrik Gregersen, Aalborg Universitet, For the Nordic Myeloma Study Group (NMSG)
  • ,
  • Niels Abildgaard, For the Nordic Myeloma Study Group (NMSG), Syddansk Universitet
  • ,
  • Pieter Sonneveld, Erasmus University Rotterdam, For the European Myeloma Network (EMN)
  • ,
  • Karen Dybkær, Aalborg Universitet

Background: Multiple 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. Methods: Patients 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. Results: Minimal 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. Conclusions: Flow-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 registration: NCT01208766

OriginalsprogEngelsk
Artikelnummer147
TidsskriftBMC Cancer
Vol/bind22
Nummer1
Antal sider11
ISSN1471-2407
DOI
StatusUdgivet - 2022

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