Other monoclonal gammopathies
A monoclonal gammopathy is a plasma cell disorder characterised by abnormal immunoglobulin synthesis resulting in the production of paraprotein. Monoclonal gammopathy of undetermined significance (MGUS), Monoclonal gammopathy of clinical significance (MGCS), Waldenströms macroglobulinaemia and heavy chain disease are included in the list of monoclonal gammopathies.
Monoclonal gammopathy of undetermined significance (MGUS)
MGUS is a benign condition, defined as the presence of paraprotein in the serum or urine of an individual with no evidence of myeloma, AL amyloidosis, Waldenströms macroglobulinaemia or other related disorders. MGUS is relatively common and likely to increase as the population ages – it is estimated that around 75% of the 6000 people diagnosed with MGUS each year in the UK are aged 65 and over.
Paraprotein is frequently identified by chance during investigations for unrelated conditions or during a health screening. MGUS is then defined by the following criteria: serum paraprotein concentration < 30 g/l; bone marrow plasma cells less than 10%, and no evidence of myeloma-related organ or tissue impairment (ROTI), and therefore no symptoms.
In most cases, MGUS does not progress to a more serious disorder but remains stable for many years. However, for a small number of patients, they can progress to other conditions such as myeloma or AL amyloidosis. The risk of progression to myeloma is 1% per year and the risk remains throughout the lifetime of that individual.
MGUS management consists of monitoring of paraprotein levels to detect progression, but there is no active treatment. This monitoring may be done in primary or secondary care, increasingly via nurse-led clinics, according to local shared care and funding agreements. Patients may be seen three or four times in the first year after diagnosis and thereafter every six months in the first few years. Follow-up should be indefinite but could be less frequent if paraproteins remain stable and the patient has no symptoms. If paraprotein levels appear to be on the rise then more frequent (3-4 monthly) check-ups are advised.
A diagnosis of MGUS can have a significant emotional impact on patients. Although benign, it can seem like a ticking time bomb, and the relative lack of contact with the healthcare team can be unsettling for patients. Nurses have an important role to play in helping them cope emotionally between appointments and ensuring they are vigilant for any development of the signs and symptoms of active myeloma or other related conditions.
Further reading
Monoclonal gammopathy of clinical significance (MGCS)
It is increasingly recognised that the presence of low level (<30g/L) paraprotein in the blood can cause complications in some patients. If this occurs in patients who fulfil the other criteria for an MGUS diagnosis, the term monoclonal gammopathy of clinical significance (MGCS) may be used. Most commonly, it is the kidneys that are affected by the circulating paraprotein, and these people are considered to have monoclonal gammopathy of renal significance (MGRS). They may suffer from symptoms such as fatigue, frothy urine, breathlessness, changes to blood pressure and/or gastrointestinal symptoms. In other people, the skin and nerves, leading to peripheral neuropathy, may be most affected.
Treatment for MGCS or MGRS will focus on treating any symptoms and complications and monitoring for disease progression. In some cases where the complications are more severe, chemotherapy, steroids or other anti-myeloma treatments may be considered, although the doses and regimes are likely to be less intense. Each patient should be considered individually.
Further reading
Waldenström’s macroglobulinaemia
Waldenström’s macroglobulinaemia (WM) is a neoplastic proliferation of plasmacytoid lymphocytes in the bone marrow, which produce an IgM paraprotein. The most common symptoms are fatigue, symptoms of hyperviscosity and neurological symptoms. About 30% of patients have Iymphadenopathy and splenomegaly, but lytic bone lesions are rare. Patients may have expanded plasma volume, anaemia, and, occasionally, congestive heart failure.
Some patients with asymptomatic WM are monitored initially, with the risk of progression to symptomatic disease 59% at 5 years. Treatment of Waldenström’s macroglobulinaemia is not as defined and is different to that of myeloma, often focusing on treating complications that have arisen in particular areas of the body. Patients should be considered for clinical trials where possible.
Further reading
Pratt et al. (2022) Diagnosis and management of Waldenström macroglobulinaemia—A British Society for Haematology guideline. British Journal of Haematology. s://doi.org/10.1111/bjh.18036
Plasma cell leukaemia
Plasma cell leukaemia (PCL) is a cancer that is characterised by unusually high levels of abnormal plasma cells in the blood – exceeding 20% of the total white blood cell count. It can start by itself (primary PCL) or it can evolve from the last stage of advanced myeloma (secondary PCL).
Primary PCL is very rare. Bone involvement is uncommon and the main feature is extramedullary disease, affecting organs such as the liver, spleen and lymph nodes.
Compared to myeloma patients, PCL patients tend to have more severe anaemia and thrombocytopenia, and higher paraprotein levels.