IgM monoclonal gammopathies of clinical significance: diagnosis and management
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 significa...
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| Vydáno v: | Haematologica (Roma) Ročník 107; číslo 9; s. 2037 - 2050 |
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| Hlavní autoři: | , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
Fondazione Ferrata Storti
01.09.2022
Ferrata Storti Foundation |
| Témata: | |
| ISSN: | 0390-6078, 1592-8721, 1592-8721 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | 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. |
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| Bibliografie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 Disclosures Contributions JK and JMIV wrote the first draft of the manuscript, SD’S, MCM, MJK, and AW equally reviewed and added critical discussions throughout the writing of the review. JK has no conflicts of interest to disclose. SD'S has received research funding, honoraria for advisory board work and conference support from Janssen and BeiGene, and honoraria for advisory board work from Sanofi. MCM has provided speakers bureau services for Medscape and BMS, consultancy for Janssen-Cilag and Gilead Sciences Netherlands B.V., sat on advisory boards for Janssen Pharmaceutica and Alnylam, and received hospitality support from Celgene. MJK has acted as a consultant for and received honoraria and travel support from Novartis and Miltenyi Biotec, has received research funding from Takeda and Celgene, has acted as a consultant for and received honoraria, travel support and research funding from Kite, a Gilead Company, and Roche, and has acted as a consultant for and received honoraria from BMS/Celgene. AW has provided consultancy services for Alexion, AstraZeneca Rare Diseases and Janssen, and has received honoraria from Celgene and Takeda, clinical trial funding from Caelum Biosciences, and research funding from Amgen. JMIV has received reimbursement of travel costs from Celgene, receives research funding from Beigene (institutional) and has participated in an advisory board as well as acted as a consultant for Sanofi (institutional honoraria) |
| ISSN: | 0390-6078 1592-8721 1592-8721 |
| DOI: | 10.3324/haematol.2022.280953 |