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

Alexander Schmitz, Rasmus Froberg Brøndum, Hans Erik Johnsen, Ulf Henrik Mellqvist, Anders Waage, Peter Gimsing, Davine Hofste op Bruinink, Vincent van der Velden, Bronno van der Holt, Markus Hansson, Niels Frost Andersen, Ulf Christian Frølund, Carsten Helleberg, Fredrik H. Schjesvold, Lucia Ahlberg, Nina Gulbrandsen, Bjorn Andreasson, Birgitta Lauri, Einar Haukas, Julie Støve BødkerAnne Stidsholt Roug, Martin Bøgsted, Marianne T. Severinsen, Henrik Gregersen, Niels Abildgaard, Pieter Sonneveld, Karen Dybkær*

*Corresponding author for this work
    1 Citation (Scopus)

    Abstract

    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

    Original languageEnglish
    Article number147
    JournalBMC Cancer
    Volume22
    Issue number1
    ISSN1471-2407
    DOIs
    Publication statusPublished - Dec 2022

    Keywords

    • Flow cytometry
    • Minimal residual disease
    • Multiple myeloma

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