Southern Derbyshire Shared Care Pathology Guidelines. Diagnosis and Management of Myeloma

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1 Southern Derbyshire Shared Care Pathology Guidelines Diagnosis and Management of Myeloma When to screen for Myeloma and related disorders Not recommended to screen the normal population Clinical Symptoms, not an exhaustive list, but could include any of the following if the cause is not known: o Unexplained Sweating o Bone Pain o Renal Impairment o Recurrent Infections o Neurological Symptoms, e.g. polyneuropathies, parasthaesia o Abnormal X-ray findings, e.g. lytic lesions, osteoporosis Any of the following pathology findings with no known explanation: o ESR > 30 mm/h o Adjusted Calcium > 2.65 mmol/l (PTH low, and no known Primary Cancer) o New case of renal impairment (CKD stages 3 to 5, i.e. egfr < 60) o Serum globulins > 48 g/l o Serum globulins < 19 g/l o Anaemia Please note that depending on the clinical details provided, the lab will perform a myeloma screen on samples that we detect with: o high or low globulins without a known cause o hypercalcaemia and a suppressed PTH without a known cause At the moment we do not automatically undertake a myeloma screen on new, unexplained cases of anaemia, raised ESR or renal impairment which we may detect. What is a Myeloma Screen? The basic Myeloma Screen consists of the following 4 tests and is performed on a serum sample (either red or gold top). Total Protein Albumin Calculated Globulins Serum Protein Electrophoresis () Authorised by Julia Forsyth Page 1 of 6

2 Serum Protein Electrophoresis () can detect an unusual protein band in the serum, a monoclonal band. These bands are also known as paraproteins. 4 outcomes are possible: Normal Polyclonal Raised Gamma Globulins Monoclonal Band (Paraprotein) Present Significantly Reduced Gamma Globulins Laboratory will measure Serum Free Light Chains (FLC) FLC Ratio Appropriate for Clinical Setting? YES Myeloma Highly Unlikely Seen in infection, inflammation or liver disease Myeloma Highly Unlikely FLC not needed. Dependent upon clinical details, Further tests may follow NO Further Testing for?myeloma/mgus will be carried out by the laboratory: Immunofixation Immunoglobulins Free Light Chains The laboratory will advise on the report whether the results suggest MGUS, Myeloma or other Lymphoproliferative Disorder and whether the patient needs referral or not, but relies on you to undertake the clinical assessment where necessary All patients with IgD, IgE and Free Light Chain only secreting abnormalities need to be referred All patients with significant immuneparesis need to be further assessed whether or not there is a paraprotein present For further detailed information and contacts see pages below Authorised by Julia Forsyth Page 2 of 6

3 Risk Stratification for MGUS patients (for further information see the shared care MGUS guideline) Paraprotein Present Any Unexplained: Hypercalcaemia Renal Impairment Anaemia Lytic lesion Osteoporosis YES to Any 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 YES to Any 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 YES to Any NO to ALL Community monitoring or Seek advice if unclear Consultant Haematologist Referral Authorised by Julia Forsyth Page 3 of 6

4 What happens if a paraprotein is detected in a myeloma screen? When a possible monoclonal band (paraprotein) has been identified it is vital to establish the nature of the band and its significance. The presence of a paraprotein may be found in the following disorders: Monoclonal Gammopathy of Undetermined Significance (MGUS) Multiple Myeloma Solitary Plasmacytoma AL amyloidosis Waldenström Macroglobulinaemia Non-Hodgkin s Lymphoma and other Β-lineage Lymphoproliferative Disorder Other Monoclonal Protein Related Disorders The laboratory will advise on the report whether the results suggest MGUS, Myeloma or other Lymphoproliferative Disorder and whether the patient needs referral or not. MGUS An MGUS is the commonest cause for the presence of a paraprotein in a patient s serum, and is a relatively common disorder in the elderly population, with a low rate of progression to malignant disease (~1% per year). Therefore the majority of patients with MGUS die of other diseases, rather than their monoclonal gammopathy. The size and type of paraprotein, in addition to other factors can help to separate patients with MGUS into those with low, intermediate and high risks of developing multiple myeloma. In low risk cases MGUS patients do not need to be referred to the Consultant Haematologist and can be managed in the community. For further information on the management of patients with MGUS please refer to the shared care guideline for MGUS. Myeloma and Other Related Disorders Where the results of further laboratory testing suggest multiple myeloma or another lymphoproliferative disorder, the laboratory report will suggest referral for a Consultant Haematologist opinion and further assessment. Useful Contacts Dr David Allotey (Consultant Haematologist) Dr Sangam Hebballi (Consultant Haematologist) Dr Ian Amott (Consultant Haematologist) Christine Morris (Haematology Specialist Nurse) Susan Robb (Haematology Specialist Nurse) Duty Biochemist Useful Website Authorised by Julia Forsyth Page 4 of 6

5 Serum Protein Immunofixation This will determine whether there is truly a monoclonal band (paraprotein) present, and identify the type of band present. The commoner types are: Heavy chains: IgG, IgM and IgA Light chains: κ (Kappa) and λ (Lambda) Results are reported as IgGκ, IgGλ, IgMκ, IgMλ, IgAκ, and IgAλ. These are usually solitary protein bands, but 2 or more bands are sometimes present, sometimes of the same heavy and light chain type, or they can be of different types. Heavy chain only and light chain only secreting disorders can also be seen. The former are quite rare, whilst the latter are relatively common (possibly up to 10-15% of all MGUS and myeloma). Where appropriate these are identified by immunofixation. In addition where appropriate we also identify the rare IgD secreting disorders and the very rare IgE disorders. Monoclonal Protein Quantitation The amount of the paraprotein also has clinical significance and is routinely determined and expressed in g/l. It is important to note that the quantity of paraprotein determined from serum protein electrophoresis (or by densitometry scanning of gels) does not always equal that of the particular immunoglobulin by conventional means (immunoassay). For example the patient may have an IgG Kappa paraprotein of 25 g/l determined by, whilst their total IgG may be higher due to the presence of polyclonal IgG present in the serum as well as the monoclonal protein. In addition in some patient s serum the monoclonal protein reacts oddly with the polyclonal antisera used to measure the total immunoglobulins, resulting in much higher or lower values compared to. This is relatively common in IgM abnormalities. Where possible it is important to use the paraprotein result by (listed on laboratory reports as S-band) to monitor the patient. In addition it is recommended to try and use the same method when monitoring a patient, or at least demonstrate comparability of results. Measurement of Total Major Immunoglobulins The quantities of IgA, IgG and IgM are also determined, as these can give extra information when classifying patients, but have particular importance in demonstrating immuneparesis, where all or some of the non-monoclonal immunoglobulins are reduced. This finding is of clinical significance when assessing these patients. Authorised by Julia Forsyth Page 5 of 6

6 The adult reference ranges for the three major immunoglobulins are: Immunoglobulin Adults < 45y Adults > 45y IgG g/l g/l IgA g/l g/l IgM g/l g/l Measurement of Free Light Chains Since quite a high percentage of myeloma can secrete light chains only, i.e. with no heavy component, it is important to look for these Free Light Chains when routinely assessing these patients. In addition, the presence or absence of free light chains is a prognostic factor is assessing potential myeloma patients. Since these are small molecular weight proteins they generally pass straight through the glomerulus and can be determined in the urine as a Bence Jones Protein (BJP). However in Derby we directly measure the Free Kappa and Lambda light chains in the serum, as this is a more sensitive marker than BJP and does not require the separate collection of a random urine sample. The quantities of Free Kappa and Free Lambda Light Chains are determined in the serum and the Kappa- Lambda ratio is then determined. If there is free light chain secreting monoclonal gammopathy present the normal ratio of Kappa to Lambda will change, giving rise to an abnormal Free Light Chain Ratio. Adult Reference Ranges are: Free Kappa = mg/l Free Lambda = mg/l Kappa/Lambda Ratio = Many situations can give rise to abnormally high free kappa and free lambda concentrations, and these are not usually significant. It is the ratio that is important in diagnosis. Small increases in the FLC ratio (up to 3.5) can be seen in renal impairment or polyclonal increases in immunoglobulins, and are not usually clinically important. When monitoring patients with light chain secreting abnormalities it is important to measure the specific Kappa or Lambda light chain rather than the ratio. 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 st Oct 2015 Dr D Allotey, Dr S Hebballi, Dr I Amott, Oct st Oct 2017 Mrs H Seddon Dr D Allotey, Dr P Blackwell, Mrs H Seddon Jan st Jan 2020 Authorised by Julia Forsyth Page 6 of 6