TY - JOUR

T1 - 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

AU - Schmitz, Alexander

AU - Brøndum, Rasmus Froberg

AU - Johnsen, Hans Erik

AU - Mellqvist, Ulf Henrik

AU - Waage, Anders

AU - Gimsing, Peter

AU - op Bruinink, Davine Hofste

AU - van der Velden, Vincent

AU - van der Holt, Bronno

AU - Hansson, Markus

AU - Andersen, Niels Frost

AU - Frølund, Ulf Christian

AU - Helleberg, Carsten

AU - Schjesvold, Fredrik H.

AU - Ahlberg, Lucia

AU - Gulbrandsen, Nina

AU - Andreasson, Bjorn

AU - Lauri, Birgitta

AU - Haukas, Einar

AU - Bødker, Julie Støve

AU - Roug, Anne Stidsholt

AU - Bøgsted, Martin

AU - Severinsen, Marianne T.

AU - Gregersen, Henrik

AU - Abildgaard, Niels

AU - Sonneveld, Pieter

AU - Dybkær, Karen

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - 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

AB - 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

KW - Flow cytometry

KW - Minimal residual disease

KW - Multiple myeloma

UR - http://www.scopus.com/inward/record.url?scp=85124249582&partnerID=8YFLogxK

U2 - 10.1186/s12885-022-09184-1

DO - 10.1186/s12885-022-09184-1

M3 - Journal article

C2 - 35123422

AN - SCOPUS:85124249582

VL - 22

JO - B M C Cancer

JF - B M C Cancer

SN - 1471-2407

IS - 1

M1 - 147

ER -