A risk-stratification model based on the initial concentration of the serum monoclonal protein and MYD88 mutation status identifies a subset of patients with IgM monoclonal gammopathy of undetermined significance at high risk of progression to Waldenström macroglobulinaemia or other lymphoproliferative disorders

Marzia Varettoni, Silvia Zibellini, Emanuela Boveri, Catherine Klersy, Chiara Candido, Sara Rattotti, Virginia V. Ferretti, Irene Defrancesco, Silvia Mangiacavalli, Maria E. Nizzoli, Elena Flospergher, Caterina Zerbi, Fabio Bergamini, Pietro Benvenuti, Marco Brociner, Gabriele Merati, Marco Paulli, Luca Arcaini

Research output: Contribution to journalArticle

Abstract

IgM monoclonal gammopathies of undetermined significance (IgM MGUS) are associated with a risk of progression to Waldenström macroglobulinaemia (WM) or other lymphoproliferative disorders (LPD) of 1–2% per year. We analysed 176 consecutive patients with IgM MGUS to evaluate risk factors for progression. With a median follow-up of 83 months (1214 person-years), 15 patients (8·5%) progressed to WM (n = 14) or marginal zone lymphoma (n = 1). The rate of progression was 1·32% per year (95% confidence interval [CI] 0·80–2·20). The serum monoclonal protein concentration and the MYD88 mutation were independent risk factors for progression (Hazard ratio [HR] 23·3, 95% CI 2·0–273·3, P = 0·012 and HR 24·4, 95% CI 2·2–275·3, P = 0·010, respectively). The cumulative incidence of progression, while considering death as a competing event, was 11·6% at 5 years and 38·0% at 10 years in MYD88-mutated patients with a serum monoclonal protein of 10 g/l or higher, as compared with 0% at 5 years and 1·1% at 10 years for patients with none or one risk factor. This risk-stratification model is able to identify a subset of patients with IgM MGUS at high risk of progression to WM or LPD who deserve a lifelong follow-up.

Original languageEnglish
JournalBritish Journal of Haematology
DOIs
Publication statusPublished - Jan 1 2019

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Monoclonal Gammopathy of Undetermined Significance
Waldenstrom Macroglobulinemia
Lymphoproliferative Disorders
Immunoglobulin M
Blood Proteins
Mutation
Confidence Intervals
Lymphoma
Incidence

Keywords

  • follow-up
  • monoclonal gammopathy of undetermined significance
  • MYD88 mutation
  • risk of progression
  • Waldenström macroglobulinaemia

ASJC Scopus subject areas

  • Hematology

Cite this

@article{c32cf6d05d9c4ad7a6b863f1563a3dec,
title = "A risk-stratification model based on the initial concentration of the serum monoclonal protein and MYD88 mutation status identifies a subset of patients with IgM monoclonal gammopathy of undetermined significance at high risk of progression to Waldenstr{\"o}m macroglobulinaemia or other lymphoproliferative disorders",
abstract = "IgM monoclonal gammopathies of undetermined significance (IgM MGUS) are associated with a risk of progression to Waldenstr{\"o}m macroglobulinaemia (WM) or other lymphoproliferative disorders (LPD) of 1–2{\%} per year. We analysed 176 consecutive patients with IgM MGUS to evaluate risk factors for progression. With a median follow-up of 83 months (1214 person-years), 15 patients (8·5{\%}) progressed to WM (n = 14) or marginal zone lymphoma (n = 1). The rate of progression was 1·32{\%} per year (95{\%} confidence interval [CI] 0·80–2·20). The serum monoclonal protein concentration and the MYD88 mutation were independent risk factors for progression (Hazard ratio [HR] 23·3, 95{\%} CI 2·0–273·3, P = 0·012 and HR 24·4, 95{\%} CI 2·2–275·3, P = 0·010, respectively). The cumulative incidence of progression, while considering death as a competing event, was 11·6{\%} at 5 years and 38·0{\%} at 10 years in MYD88-mutated patients with a serum monoclonal protein of 10 g/l or higher, as compared with 0{\%} at 5 years and 1·1{\%} at 10 years for patients with none or one risk factor. This risk-stratification model is able to identify a subset of patients with IgM MGUS at high risk of progression to WM or LPD who deserve a lifelong follow-up.",
keywords = "follow-up, monoclonal gammopathy of undetermined significance, MYD88 mutation, risk of progression, Waldenstr{\"o}m macroglobulinaemia",
author = "Marzia Varettoni and Silvia Zibellini and Emanuela Boveri and Catherine Klersy and Chiara Candido and Sara Rattotti and Ferretti, {Virginia V.} and Irene Defrancesco and Silvia Mangiacavalli and Nizzoli, {Maria E.} and Elena Flospergher and Caterina Zerbi and Fabio Bergamini and Pietro Benvenuti and Marco Brociner and Gabriele Merati and Marco Paulli and Luca Arcaini",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/bjh.16086",
language = "English",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley & Sons, Ltd (10.1111)",

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TY - JOUR

T1 - A risk-stratification model based on the initial concentration of the serum monoclonal protein and MYD88 mutation status identifies a subset of patients with IgM monoclonal gammopathy of undetermined significance at high risk of progression to Waldenström macroglobulinaemia or other lymphoproliferative disorders

AU - Varettoni, Marzia

AU - Zibellini, Silvia

AU - Boveri, Emanuela

AU - Klersy, Catherine

AU - Candido, Chiara

AU - Rattotti, Sara

AU - Ferretti, Virginia V.

AU - Defrancesco, Irene

AU - Mangiacavalli, Silvia

AU - Nizzoli, Maria E.

AU - Flospergher, Elena

AU - Zerbi, Caterina

AU - Bergamini, Fabio

AU - Benvenuti, Pietro

AU - Brociner, Marco

AU - Merati, Gabriele

AU - Paulli, Marco

AU - Arcaini, Luca

PY - 2019/1/1

Y1 - 2019/1/1

N2 - IgM monoclonal gammopathies of undetermined significance (IgM MGUS) are associated with a risk of progression to Waldenström macroglobulinaemia (WM) or other lymphoproliferative disorders (LPD) of 1–2% per year. We analysed 176 consecutive patients with IgM MGUS to evaluate risk factors for progression. With a median follow-up of 83 months (1214 person-years), 15 patients (8·5%) progressed to WM (n = 14) or marginal zone lymphoma (n = 1). The rate of progression was 1·32% per year (95% confidence interval [CI] 0·80–2·20). The serum monoclonal protein concentration and the MYD88 mutation were independent risk factors for progression (Hazard ratio [HR] 23·3, 95% CI 2·0–273·3, P = 0·012 and HR 24·4, 95% CI 2·2–275·3, P = 0·010, respectively). The cumulative incidence of progression, while considering death as a competing event, was 11·6% at 5 years and 38·0% at 10 years in MYD88-mutated patients with a serum monoclonal protein of 10 g/l or higher, as compared with 0% at 5 years and 1·1% at 10 years for patients with none or one risk factor. This risk-stratification model is able to identify a subset of patients with IgM MGUS at high risk of progression to WM or LPD who deserve a lifelong follow-up.

AB - IgM monoclonal gammopathies of undetermined significance (IgM MGUS) are associated with a risk of progression to Waldenström macroglobulinaemia (WM) or other lymphoproliferative disorders (LPD) of 1–2% per year. We analysed 176 consecutive patients with IgM MGUS to evaluate risk factors for progression. With a median follow-up of 83 months (1214 person-years), 15 patients (8·5%) progressed to WM (n = 14) or marginal zone lymphoma (n = 1). The rate of progression was 1·32% per year (95% confidence interval [CI] 0·80–2·20). The serum monoclonal protein concentration and the MYD88 mutation were independent risk factors for progression (Hazard ratio [HR] 23·3, 95% CI 2·0–273·3, P = 0·012 and HR 24·4, 95% CI 2·2–275·3, P = 0·010, respectively). The cumulative incidence of progression, while considering death as a competing event, was 11·6% at 5 years and 38·0% at 10 years in MYD88-mutated patients with a serum monoclonal protein of 10 g/l or higher, as compared with 0% at 5 years and 1·1% at 10 years for patients with none or one risk factor. This risk-stratification model is able to identify a subset of patients with IgM MGUS at high risk of progression to WM or LPD who deserve a lifelong follow-up.

KW - follow-up

KW - monoclonal gammopathy of undetermined significance

KW - MYD88 mutation

KW - risk of progression

KW - Waldenström macroglobulinaemia

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U2 - 10.1111/bjh.16086

DO - 10.1111/bjh.16086

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JO - British Journal of Haematology

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