Khwaja, J;
D'Sa, S;
Minnema, MC;
Kersten, MJ;
Wechalekar, A;
Vos, JM;
(2022)
IgM monoclonal gammopathies of clinical significance: diagnosis and management.
Haematologica
, 107
(9)
pp. 2037-2050.
10.3324/haematol.2022.280953.
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Abstract
IgM monoclonal gammopathy of undetermined significance is a pre-malignant condition for Waldenström macroglobulinemia and other B-cell malignancies, defined by asymptomatic circulating IgM monoclonal protein below 30 g/L with a lymphoplasmacytic bone marrow infiltration of less than 10%. A significant proportion, however, develop unique immunological and biochemical manifestations related to the monoclonal protein itself in the absence of overt malignancy and are termed IgM-related disorders or, more recently, monoclonal gammopathy of clinical significance. The indication for treatment in affected patients is dictated by the pathological characteristics of the circulating IgM rather than the tumor itself. The clinical workup and treatment options vary widely and differ from those for Waldenström macroglobulinemia. The aim of this review is to alert clinicians to IgM monoclonal gammopathy of clinical significance and to provide practical guidance on when to screen for these phenotypes. We discuss clinical characteristics, the underlying clonal profile, diagnostic workup and treatment considerations for five important subtypes: cold agglutinin disease, type I and II cryoglobulinemia, IgM-associated peripheral neuropathy, Schnitzler syndrome and IgM-associated AL amyloidosis. The inhibition of the pathogenic effects of the IgM has led to great success in cold agglutinin disease and Schnitzler syndrome, whereas the other treatments are centered on eradicating the underlying clone. Treatment approaches in cryoglobulinemia and IgM-associated peripheral neuropathy are the least well developed. A multidisciplinary approach is required, particularly for IgM-related neuropathies and Schnitzler syndrome. Future work exploring novel, clone-directed agents and pathogenic IgM-directed therapies is welcomed.
| Type: | Article |
|---|---|
| Title: | IgM monoclonal gammopathies of clinical significance: diagnosis and management |
| Location: | Italy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3324/haematol.2022.280953 |
| Publisher version: | https://doi.org/10.3324/haematol.2022.280953 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc/4.0/deed.en |
| Keywords: | Anemia, Hemolytic, Autoimmune, Cryoglobulinemia, Humans, Immunoglobulin M, Lymphoma, B-Cell, Paraproteinemias, Schnitzler Syndrome, Waldenstrom Macroglobulinemia |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10156159 |
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