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Monoclonal gammopathy of undetermined significance

Key sources
The following summarized guidelines for the evaluation and management of monoclonal gammopathy of undetermined significance are prepared by our editorial team based on guidelines from the British Society for Haematology (BSH 2023), the American Society for Clinical Pathology (ASCP/CAP/AACC 2022), the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2020), the Amyloidosis Research Consortium (ARC 2019), the American Society of Clinical Oncology (ASCO 2018), and the European Myeloma Network (EMN 2014).


1.Screening and diagnosis

Indications for screening: insufficient evidence to recommend screening for MGUS.
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2.Classification and risk stratification

Risk assessment: as per BSH 2023 guidelines, obtain risk stratification (either in primary care or secondary care) using a validated published model, preferably models not involving a bone marrow examination, to optimize initial management and further follow-up in patients with newly diagnosed MGUS.

3.Diagnostic investigations

Laboratory testing: as per BSH 2023 guidelines, obtain immunofixation upon detection of a new M protein to confirm the type of monoclonal protein. Obtain serum free light chain assay to measure free light chain levels and calculate the free light chain ratio.
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4.Diagnostic procedures

Bone marrow biopsy
As per BSH 2023 guidelines:
Do not perform bone marrow examination in patients with newly diagnosed low or low-intermediate-risk MGUS.
Perform bone marrow examination at diagnosis in patients with high-intermediate or high-risk MGUS.

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5.Medical management

Bisphosphonates: as per ASCO 2018 guidelines, do not use bisphosphonates in patients with MGUS unless osteopenia/osteoporosis is present.

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6.Specific circumstances

Kidney transplant candidates
Avoid excluding patients with MGUS from kidney transplantation, taking into consideration the higher risk of post-transplant lymphoproliferative disease and other hematological malignancies and discussing it with the candidates.
Obtain a careful evaluation for other types of plasma cell disorders before kidney transplantation in patients with MGUS.

7.Patient education

General counseling: provide clear information and psychological support at diagnosis and during follow-up in patients with MGUS.

8.Follow-up and surveillance

Follow-up: as per BSH 2023 guidelines, obtain appropriate blood tests (CBC, creatinine, serum calcium, paraprotein, and serum free light chain levels) 6 months after diagnosis and annually thereafter in patients with newly diagnosed MGUS. Consider extending the interval in low-risk MGUS and reducing further investigations in patients with a short life expectancy.
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