Southern Derbyshire Shared Care Pathology Guidelines MGUS (Monoclonal Gammopathy of Undetermined Significance) Purpose of guideline This guideline provides information about the risk stratification of patients diagnosed with MGUS and their management. Definition The presence of a monoclonal protein (also known as a paraprotein), in the serum or urine of an individual with no evidence of multiple myeloma, AL amyloidosis, Waldenstrom macroglobulinaemia or other related disorder. Paraproteins can be detected in the serum of about 1% of the population, and are frequently detected as a result of a myeloma screen (see shared care guideline for myeloma for further information). MGUS is uncommon below the age of 50 years and the prevalence increases with age. It is important to identify and monitor those patients at highest risk of progression to significant disease, whilst avoiding unnecessary follow-up of patients at low risk of progression. Diagnostic criteria for MGUS Paraprotein in serum <30g/L Bone marrow clonal plasma cells <10% and low level plasma cell infiltration in a trephine biopsy No myeloma-related organ or tissue impairment (including bone lesions or symptoms) No evidence of other B-cell lymphoproliferative disorder or light chain associated amyloidosis or other light chain, heavy chain or immunoglobulinassociated tissue damage Risk stratification for MGUS Three parameters can separate patients with MGUS into those with low, intermediate and high risks of developing multiple myeloma. They are the serum paraprotein level, the immunoglobulin (Ig) isotype and the free light chain (FLC) ratio. The intermediate grouping is sub-divided into low-intermediate and highintermediate. Since the majority of patients with MGUS arise from diagnostic testing done in the laboratory, we will undertake the first stage of the risk stratification, to enable the patient to follow the appropriate care pathway. It is vital at this stage to ensure those patients with a strong likelihood of myeloma or serious lymphoproliferative disorders are referred quickly to a Consultant Haematologist for further assessment. For further details please see the shared care guideline for myeloma. Authorised by Julia Forsyth Page 1 of 5
Risk Group Low risk Serum Paraprotein <15g/L IgG isotype Appropriate FLC ratio Low-intermediate risk Presence of an IgA or IgM isotype (<10g/L) OR High-intermediate risk Presence of an IgA or IgM isotype (<10g/L) AND High risk If IgG, Paraprotein >15g/L If IgA or IgM, Paraprotein >10g/L 20 year risk of progression to myeloma (%) 5 21 37 58 Please note that the presence of an IgM paraprotein may be associated with lymphoma or other lymphoproliferative disorders please check for B symptoms including weight loss, fever, night sweats, lymphadenopathy or organomegaly. Any patient with symptoms, signs or results suggestive of myeloma, other lymphoproliferative disorders or AL amyloidosis needs to be dealt with outside of this stratification listing, and needs to be seen by a Consultant Haematologist. Further Assessment Low and Low-intermediate Risk Groups These groups have the lowest transformation rate, and the majority of patients can be managed well in the community as detailed below, without the need for further invasive testing or Consultant referral. You can establish whether your patient falls into these groups yourself, or alternatively write/telephone Consultant Haematologists Dr Allotey, Dr Hebballi or Dr Amott or a Haematology Nurse Specialist (Sue Robb or Chris Skeet) to request for advice only on the further management of the patient. High-Intermediate and High Risk Groups These patients need to be referred to Dr Allotey, Dr Hebballi or Dr Amott. The high risk patients will be seen once by a Consultant Haematologist for further assessment, and then followed up in the CNS Teleclinic. The high-intermediate risk patients will also be followed up in the CNS Teleclinic after consultant haematologist review of their details. Some of the intermediate risk patients may also need further testing and assessment. Authorised by Julia Forsyth Page 2 of 5
Management of low and low-intermediate risk patients in primary care Patients should be assessed every 3 to 4 monthly initially. They should specifically be asked about bone pain and episodes of infection. Blood tests should be carried out prior to each assessment as follows: Quantitation of the paraprotein and immunoglobulin levels Serum free light chains Full blood count Urea and electrolytes Corrected calcium If the patient is stable after 3 visits, the appointment frequency can be reduced to 6 monthly for two more visits then annually thereafter. Patients should be re-referred to the consultant clinic if they develop any of the following: Bone symptoms Infection New bone pain or compression fracture without other cause >2 significant bacterial infections within 12 months Anaemia Renal Function Hypercalcaemia Hb <100g/L or 20g/L below reference range No blood loss, normal haematinics >25% increase in creatinine OR creatinine >173 umol/l without other cause >25% increase in calcium OR calcium >2.75 mmol/l without other cause Paraprotein >25% increased concentration AND total increase >5g In cases of IgM paraprotein, refer patients with any new symptoms of weight loss, night sweats, fever, lymphadenopathy or organomegaly. Patient information An excellent patient information sheet is available on the Myeloma UK website: www.myeloma.org.uk/information/myeloma-uk-publications-list/other-related conditions/monoclonal-gammopathy-of-undetermined-significance-mgus-infosheet/ Reference UK Myeloma Forum (UKMF) and Nordic Myeloma Study Group (NMSG): guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS). British Journal of Haematology, 147, 22-42. Useful Contacts Consultant Haematologist 01332 783378 Christine Skeet (Haematology Specialist Nurse) 07879 115881 Sue Robb (Haematology Specialist Nurse) 07825 342918 Duty Biochemist 01332 789383 Authorised by Julia Forsyth Page 3 of 5
MGUS Risk Stratification Paraprotein Present Any Unexplained: Hypercalcaemia Renal Impairment Anaemia Lytic lesion Osteoporosis Paraprotein >30 g/l Very Abnormal FLC ratio (>8 or <0.1) Free Kappa or Free Lambda >100mg/L Immuneparesis & other abnormal findings Laboratory will identify patients and stratify patients on report Significant Disease Probable Urgent Consultant Haematologist Referral NO to ALL MGUS RISK FACTORS: IgG Paraprotein >15 g/l OR IgA or IgM Paraprotein >10 g/l NO to ALL Community monitoring or Seek advice if unclear Consultant Haematologist Referral Authorised by Julia Forsyth Page 4 of 5
Authors: Dr David Allotey, Dr Chris Millar, Dr Nigel Lawson, July 2011 Reviewed by: Date: Expiry date: Dr D Allotey, Dr P Blackwell, Mrs H Seddon Oct 2013 31 st Oct 2015 Dr D Allotey, Dr S Hebballi, Dr I Amott, Oct 2015 31 st Oct 2017 Mrs H Seddon, Ms J Forsyth Dr D Allotey, Dr P Blackwell, Mrs H Seddon Jan 2018 31 st Jan 2020 Authorised by Julia Forsyth Page 5 of 5