Monoclonal gammopathy of undetermined significance with multiple paraproteins: A population‐based screening study

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is the precursor of multiple myeloma (MM) and related disorders. MGUS is characterized by asymptomatic paraproteinemia. In some cases, multiple paraproteins can be identified but the clinical implications of this phenomenon are poorl...

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Main Authors: Sæmundur Rögnvaldsson, Jón Þ. Óskarsson, Sigrun Thorsteinsdóttir, Malin Hultcrantz, Robert Palmason, Ingigerdur S. Sverrisdottir, Elias Eythorsson, Thorir E. Long, Isleifur Olafsson, Ingunn Thorsteinsdottir, Brynjar Vidarsson, Pall T. Onundarson, Bjarni A. Agnarsson, Margret Sigurdardottir, Asbjorn Jonsson, Brian G. M. Durie, Stephen Harding, Ola Landgren, Thorvardur J. Love, Sigurdur Y. Kristinsson
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:HemaSphere
Online Access:https://doi.org/10.1002/hem3.70046
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author Sæmundur Rögnvaldsson
Jón Þ. Óskarsson
Sigrun Thorsteinsdóttir
Malin Hultcrantz
Robert Palmason
Ingigerdur S. Sverrisdottir
Elias Eythorsson
Thorir E. Long
Isleifur Olafsson
Ingunn Thorsteinsdottir
Brynjar Vidarsson
Pall T. Onundarson
Bjarni A. Agnarsson
Margret Sigurdardottir
Asbjorn Jonsson
Brian G. M. Durie
Stephen Harding
Ola Landgren
Thorvardur J. Love
Sigurdur Y. Kristinsson
author_facet Sæmundur Rögnvaldsson
Jón Þ. Óskarsson
Sigrun Thorsteinsdóttir
Malin Hultcrantz
Robert Palmason
Ingigerdur S. Sverrisdottir
Elias Eythorsson
Thorir E. Long
Isleifur Olafsson
Ingunn Thorsteinsdottir
Brynjar Vidarsson
Pall T. Onundarson
Bjarni A. Agnarsson
Margret Sigurdardottir
Asbjorn Jonsson
Brian G. M. Durie
Stephen Harding
Ola Landgren
Thorvardur J. Love
Sigurdur Y. Kristinsson
author_sort Sæmundur Rögnvaldsson
collection DOAJ
description Abstract Monoclonal gammopathy of undetermined significance (MGUS) is the precursor of multiple myeloma (MM) and related disorders. MGUS is characterized by asymptomatic paraproteinemia. In some cases, multiple paraproteins can be identified but the clinical implications of this phenomenon are poorly understood. In this study, we aim to inform the approach to this challenging MGUS subgroup by utilizing data from iStopMM, a population‐based screening study and randomized trial of follow‐up strategies. In total, 75,422 Icelanders over the age of 40 were screened for MGUS with 3389 (4.4%) having at least one paraprotein of whom 303 (9%) had multiple paraproteins. IgM paraproteins were more common in those with multiple paraproteins (49% vs. 27% of paraproteins, p < 0.001), and IgM and non‐IgM paraproteins frequently co‐occurred (60% of cases). Two‐thirds of these participants were randomized to active follow‐up where only 31% of multiple paraproteins were persistent. Paraprotein concentrations were mostly independent, and although progression events were few, the progression rate was similar between those with multiple paraproteins and a single paraprotein. In a next‐generation flow cytometry (NGF) sub‐study, two phenotypically distinct aberrant plasma cell populations could be identified in some with multiple paraproteins. The findings suggest that multiple paraproteins often reflect independent ongoing disease processes that should be monitored independently but otherwise treated similarly to other MGUS cases. Specifically, the findings highlight the need for independent monitoring of IgM and non‐IgM paraproteins in these individuals. The study provides novel insights into the management of this understudied MGUS subset.
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spelling doaj-art-e39ffd6a2bd242339dfacb71c3812cb52025-08-20T02:23:00ZengWileyHemaSphere2572-92412024-11-01811n/an/a10.1002/hem3.70046Monoclonal gammopathy of undetermined significance with multiple paraproteins: A population‐based screening studySæmundur Rögnvaldsson0Jón Þ. Óskarsson1Sigrun Thorsteinsdóttir2Malin Hultcrantz3Robert Palmason4Ingigerdur S. Sverrisdottir5Elias Eythorsson6Thorir E. Long7Isleifur Olafsson8Ingunn Thorsteinsdottir9Brynjar Vidarsson10Pall T. Onundarson11Bjarni A. Agnarsson12Margret Sigurdardottir13Asbjorn Jonsson14Brian G. M. Durie15Stephen Harding16Ola Landgren17Thorvardur J. Love18Sigurdur Y. Kristinsson19Faculty of Medicine University of Iceland Reykjavik IcelandFaculty of Medicine University of Iceland Reykjavik IcelandFaculty of Medicine University of Iceland Reykjavik IcelandMyeloma Service, Department of Medicine Memorial Sloan‐Kettering Cancer Center New York New York USAFaculty of Medicine University of Iceland Reykjavik IcelandFaculty of Medicine University of Iceland Reykjavik IcelandFaculty of Medicine University of Iceland Reykjavik IcelandFaculty of Medicine University of Iceland Reykjavik IcelandLandspítali University Hospital Reykjavik IcelandLandspítali University Hospital Reykjavik IcelandLandspítali University Hospital Reykjavik IcelandFaculty of Medicine University of Iceland Reykjavik IcelandFaculty of Medicine University of Iceland Reykjavik IcelandLandspítali University Hospital Reykjavik IcelandDepartment of Radiology Akureyri Hospital Akureyri IcelandDivision of Hematology/Oncology Samuel‐Oschin Comprehensive Cancer Institute, Cedar‐Sinai Outpatient Cancer Center Los Angeles California USAThe Binding Site Ltd. Birmingham, West‐Midlands UKMyeloma Program, Department of Medicine, Sylvester Comprehensive Cancer Center Univeristy of Miami Florida USAFaculty of Medicine University of Iceland Reykjavik IcelandFaculty of Medicine University of Iceland Reykjavik IcelandAbstract Monoclonal gammopathy of undetermined significance (MGUS) is the precursor of multiple myeloma (MM) and related disorders. MGUS is characterized by asymptomatic paraproteinemia. In some cases, multiple paraproteins can be identified but the clinical implications of this phenomenon are poorly understood. In this study, we aim to inform the approach to this challenging MGUS subgroup by utilizing data from iStopMM, a population‐based screening study and randomized trial of follow‐up strategies. In total, 75,422 Icelanders over the age of 40 were screened for MGUS with 3389 (4.4%) having at least one paraprotein of whom 303 (9%) had multiple paraproteins. IgM paraproteins were more common in those with multiple paraproteins (49% vs. 27% of paraproteins, p < 0.001), and IgM and non‐IgM paraproteins frequently co‐occurred (60% of cases). Two‐thirds of these participants were randomized to active follow‐up where only 31% of multiple paraproteins were persistent. Paraprotein concentrations were mostly independent, and although progression events were few, the progression rate was similar between those with multiple paraproteins and a single paraprotein. In a next‐generation flow cytometry (NGF) sub‐study, two phenotypically distinct aberrant plasma cell populations could be identified in some with multiple paraproteins. The findings suggest that multiple paraproteins often reflect independent ongoing disease processes that should be monitored independently but otherwise treated similarly to other MGUS cases. Specifically, the findings highlight the need for independent monitoring of IgM and non‐IgM paraproteins in these individuals. The study provides novel insights into the management of this understudied MGUS subset.https://doi.org/10.1002/hem3.70046
spellingShingle Sæmundur Rögnvaldsson
Jón Þ. Óskarsson
Sigrun Thorsteinsdóttir
Malin Hultcrantz
Robert Palmason
Ingigerdur S. Sverrisdottir
Elias Eythorsson
Thorir E. Long
Isleifur Olafsson
Ingunn Thorsteinsdottir
Brynjar Vidarsson
Pall T. Onundarson
Bjarni A. Agnarsson
Margret Sigurdardottir
Asbjorn Jonsson
Brian G. M. Durie
Stephen Harding
Ola Landgren
Thorvardur J. Love
Sigurdur Y. Kristinsson
Monoclonal gammopathy of undetermined significance with multiple paraproteins: A population‐based screening study
HemaSphere
title Monoclonal gammopathy of undetermined significance with multiple paraproteins: A population‐based screening study
title_full Monoclonal gammopathy of undetermined significance with multiple paraproteins: A population‐based screening study
title_fullStr Monoclonal gammopathy of undetermined significance with multiple paraproteins: A population‐based screening study
title_full_unstemmed Monoclonal gammopathy of undetermined significance with multiple paraproteins: A population‐based screening study
title_short Monoclonal gammopathy of undetermined significance with multiple paraproteins: A population‐based screening study
title_sort monoclonal gammopathy of undetermined significance with multiple paraproteins a population based screening study
url https://doi.org/10.1002/hem3.70046
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