An Update on Monoclonal Gammopathy and Neuropathy

Ramchandren, Sindhu; Lewis, Richard A.

doi:10.1007/s11910-011-0237-4

Cited by 69 publications

(72 citation statements)

References 82 publications

(67 reference statements)

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“…2 The most common paraprotein in patients with peripheral neuropathy is IgM, which is frequently found in MGUS or WM, 3 while IgG is usually associated with MM, POEMS syndrome, or AL. About 30% of the patients with paraproteinemia who present with peripheral neuropathy have MM, POEMS syndrome, AL, lymphoma, or another plasma cell disorder, while the remainder have MGUS.…”

Section: Epidemiologymentioning

confidence: 99%

Paraproteinemic neuropathy

Pyun

Kim

2017

Ann Clin Neurophysiol

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Paraproteinemia is caused by a proliferation of monoclonal plasma cells or B lymphocytes. Approximately 10% of idiopathic neuropathies are associated with paraproteinemia, where a certain paraprotein acts like an antibody targeted at constituents of myelin or axolemma in peripheral nerves. The relationship between paraproteinemia and peripheral neuropathy remains unclear despite this being of interest for a long time. Neurologists frequently find paraproteinemia during laboratory examinations of patients presenting with peripheral neuropathy, especially in the elderly. The possibility of a relationship with paraproteinemia should be considered in cases without an explainable cause. We review the causal association between paraproteinemia and neuropathy as well as clinical, laboratory, and electrophysiologic features, and the treatment options for paraproteinemic neuropathy.

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Section: Epidemiologymentioning

confidence: 99%

Paraproteinemic neuropathy

Pyun

Kim

2017

Ann Clin Neurophysiol

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“…However, the IgM M-protein can also be directed to other neural antigens including GD1b ganglioside, sulphatide, and chondroitin sulphate, thus leading to immune-mediated nerve damage. 77 Rituximab is effective in part of the patients with IgM MGUS-associated neuropathy. 77,78 The association between IgA and IgG MGUS and neuropathy is less clear, and MGUS may be an incidental finding without relation- …”

Section: Neurological Diseasesmentioning

confidence: 99%

“…77 Rituximab is effective in part of the patients with IgM MGUS-associated neuropathy. 77,78 The association between IgA and IgG MGUS and neuropathy is less clear, and MGUS may be an incidental finding without relation- …”

Section: Neurological Diseasesmentioning

confidence: 99%

“…ship to the neuropathy, 77 when AL amyloidosis and POEMS syndrome have been excluded. Especially, in case of neuropathy associated with monoclonal gammopathy with a rapidly progressive disease course an underlying hematologic malignancy has to excluded.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

“…77,78 The association between IgA and IgG MGUS and neuropathy is less clear, and MGUS may be an incidental finding without relation- …”

mentioning

confidence: 99%

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The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network

et al. 2014

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Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; lightchain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nClinical relevance of MGUS haematologica | 2014; 99(6) 985 Figure 1. Model for the mechanisms that contribute to the development and progression of MGUS. Obesity, exposure to pesticides, radiation exposure, and personal history of autoimmune diseases, inflammatory conditions and infections are associated with an increased risk of MGUS. In addition, there is a genetic predisposition to MGUS. (A) Primary immunoglobulin heavy chain (IgH) translocations with 5 recurrent chromosomal partners (4p16, 6p21, 11q13, 16q23, 20q11) and hyperdiploidy are early events and associated with the initiation of limited clonal plasma cell proliferation in non-IgM MGUS. Acquisition of secondary chromosomal abnormalities (such as deletions of (parts of) chromosomes or secondary chromosomal translocations) and mutations involving individual genes results in the stepwise progression from MGUS to newly diagnosed symptomatic MM, and finally aggressive forms of MM such as sPCL or extramedullary MM. During this process there is a progressive replacement of normal/polyclonal plasma cells (orange) by clonal plasma cells (blue). Progression of the plasma cell disorder is also accompanied by altered interactions of the tumor cells with various components of their microenvironment such as osteoclasts, endothelial cells, and cells of the immune system. Recent evidence suggests the presence of intraclonal heterogeneity in MGUS, adding a further level of genetic compl...

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Waldenström macroglobulinemia: 2021 update on diagnosis, risk stratification, and management

Gertz

2021

American J Hematol

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Disease Overview: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. Diagnosis: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in the majority of IgM MGUS patients. Risk Stratification: Age, hemoglobin level, platelet count, β 2 microglobulin, LDH and monoclonal IgM concentrations are characteristics that are predictive of outcomes. Risk-Adapted Therapy: Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or ibrutinib. Purine nucleoside analogues are active but usage is declining in favor of less toxic alternatives. The preferred Mayo Clinic induction is rituximab and bendamustine. Management of Refractory Disease: Bortezomib, fludarabine, thalidomide, everolimus, Bruton Tyrosine Kinase inhibitors, carfilzomib, lenalidomide, and bendamustine have all been shown to have activity in relapsed WM. Given WM's natural history, reduction of therapy toxicity is an important part of treatment selection. PATIENT A 55-year-old male was found to have an IgM monoclonal gammopathy in January 2001. He was observed until November 2006 when his IgM level climbed to 9135 mg/dL. He was treated with rituximab, bortezomib and dexamethasone for 4 months. Treatment was interrupted due to neuropathy, but the IgM level fell to 1150 mg/dL. He was observed until April 2011. At the time of progression his IgM was 11 500 mg/dL and he was treated with single agent rituximab. At that time he was found to have acquired von Willebrand disease. Rituximab failed to produce a minor response so he was placed on a trial of bendamustine, lenalidomide and rituximab. His response lasted less than 1 year. In 2014 he was placed on an experimental trial of oprozomib. This resulted in a response of 5 years duration. At relapse in August of 2019 he was placed on a trial of ixazomib and ibrutinib. Ixazomib was poorly tolerated due to diarrhea and he continued on ibrutinib alone. He has now been on ibrutinib 15 months and has achieved a very good partial response.

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An Update on Monoclonal Gammopathy and Neuropathy

Cited by 69 publications

References 82 publications

Paraproteinemic neuropathy

Paraproteinemic neuropathy

The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network

Waldenström macroglobulinemia: 2021 update on diagnosis, risk stratification, and management

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