Myeloma NS MOM

 Map of Medicine is not responsible for the correctness or accuracy of any content uploaded, referred to or linked to from the system.

Efforts are made to ensure the accuracy and agreement of these guidelines. However, we cannot guarantee this. This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer, in accordance with the mental capacity act, and informed by the summary of product characteristics of any drugs they are considering. Practitioners are required to perform their duties in accordance with the law and their regulators and nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties

Scope:

• investigation and initial management of patients with paraproteinaemias in primary care
• indications for specialist referral and management
• topics:
  • identification of paraproteinaemias
  • conditions associated with paraproteinaemias
  • diagnostic tests
  • referral pathways

Definition:

A paraprotein (monoclonal band, M-protein) is a monoclonal excess of immunoglobulin produced by plasma cells or other mature B cells.

A paraprotein conventionally refers to a monoclonal band identified by serum electrophoresis (intact immunoglobulin made up of heavy and light chains).

This pathway also refers to abnormal light chain bands in the serum (serum free light chains) or urine (Bence Jones protein) which can occur alongside or independent of an intact immunoglobulin paraprotein.

For a simple description on immunoglobulin abnormalities and light chains see http://www.cancerresearchuk.org/about-cancer/myeloma/types

Associated conditions and incidence:

Multiple myeloma:

• incidence 7.0 per 100,000 males, 5.9 per 100,000 females in UK
• neoplastic proliferation of bone marrow plasma cells
• most commonly IgG or IgA paraproteins
• rarely IgD or IgE
• exceptionally IgM
• approximately 15% light chain only
• approximately 3% non-secretory

Monoclonal gammopathy of undetermined significance (MGUS):

• incidence 16 per 100,000 all ages, 100 per 100,00 over age of 70
• prevalence 5% over age of 80
• see MGUS section for full details
• most commonly IgG, IgA or IgM

Solitary extramedullary plasmacytoma (SEM) and solitary plasmacytoma of bone (SBP):

• neoplastic proliferation of plasma cells in extramedullary soft tissue e.g. mucosa (SEM) or single bone lesion (SPB) without widespread bone marrow infiltration
• paraprotein isotype as myeloma

Light chain (AL) amyloidosis:

• associated with abnormal light chain deposition with or without evidence of underlying symptomatic myeloma
• most cases do not have intact immunoglobulin paraprotein
• most cases have clonal plasma cells in bone marrow

Waldenström’s macroglobulinaemia:

• neoplastic proliferation of mature B cells and plasma cells in bone marrow, spleen and/or lymph nodes
• associated with IgM paraproteins
• occasionally abnormal light chains in serum or urine
• not associated with lytic bone disease

Risk factors for paraproteinaemias:

• increasing incidence with age
• increased incidence in African-Caribbean ethnic groups
• environmental factors:
  • HIV
  • autoimmune disease
  • weak association with radiation, petrochemicals and agricultural chemicals
• almost all cases idiopathic

References:

Bird J, Behrens J, Westin J, Turesson I, Drayson M, Beetham R, D’Sa S, Soutar R, Waage A, Gulbrandsen N, Gregersen H, Low E, Writing group: On behalf of the Haemato-oncology Task Force of the British Committee for Standards in Haematology, UK Myeloma Forum and NordicMyeloma Study GroupUK 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) Br J Haematol 2009; 147: 22–42

BCSH and UKMF Guidelines on the Management and Diagnosis of Multiple Myeloma Sept 2010.

National Institute for Health and Clinical Excellence (NICE). Guidance on cancer services: improving outcomes in haemato-oncology cancer - the manual. London: NICE; 2003.

• 'Myeloma' (URL) from Cancer Research UK at http://www.cancerresearchuk.org/
• 'Myeloma' (URL) from Macmillan Cancer Support at http://www.macmillan.org.uk

 NSCCG Sign off form Jan 2018

Updated in line with NICE Guideline NG12: Suspected cancer: recognition and referral to coincide with updated  BNSSG 2WW Referral forms

Myeloma NSCCG Sign Off Form Sept 2016

 Symptoms which should trigger consideration of myeloma include:

• bone disease (common):
  • bone pain especially non-lumbar back pain (e.g. thoracic)
  • pathological fracture or low impact fracture
  • spinal cord compression
• recurrent or persistent bacterial infection (common)
• hyperviscosity syndrome (very rare in myeloma, more typically associated with Waldenström’s macroglobulinaemia):
  • spontaneous bleeding
  • visual impairment
  • neurological symptoms, including vertigo, headache, ataxia, hearing loss, seizures, coma
  • shortness of breath
  • fatigue and anorexia

 Serum paraproteins may be identified by the incidental finding of raised total protein when a blood test is carried out for a condition other than suspected myeloma.

Other laboratory abnormalities that may suggest myeloma include:

• anaemia
• unexplained renal impairment
• hypercalcaemia
• raised ESR/ viscosity / CRP

 Globulins are the main contributor to the total plasma protein that is not accounted for by albumin. An elevated globulin can be inferred when there is a high total protein. When the non albumin fraction of the total protein exceeds the normal range, then it is likely that excess serum globulin (gammopathy) is responsible.

There are many causes of raised serum globulin, including transient increases associated with acute infection and more prolonged increases seen with chronic inflammatory disorders or chronic infections such as HIV or TB.

Differentiating polyclonal gammopathy that occurs in inflammatory conditions from monoclonal gammopathy, which arises from plasma cell dyscrasias, requires serum electrophoresis.

 A myeloma screen includes:

• Full blood count
• renal function
• calcium
• serum protein electrophoresis
• urinary BJP

 Serum immunoglobulins and protein electrophoresis should be considered if there is clinical suspicion of a paraprotein-related disorder, such as:

• unexplained anaemia or other cytopenia
• hypercalcaemia (especially if plasma ALP is normal)
• unexplained renal failure
• unexplained raised ESR / viscosity / CRP
• pathological fracture or low-impact fracture

Initially request serum immunoglobulins.

It is important to remember that myeloma can present without monoclonal gammopathy in blood. Such cases may be identified by light chain secretion in urine (Bence-Jones protein) with the majority of these cases also having low serum immunoglobulins (immune paresis) and/or serum free light chains.

For a simple description on immunoglobulin abnormalities and light chains see http://www.cancerresearchuk.org/about-cancer/myeloma/types

Approximately 3% of myeloma cases will have no detectable paraprotein in the blood or abnormal light chains in blood or urine (non-secretory myeloma). Bone marrow aspiration is the usual route of diagnosis.

Serum free light chains are not currently available in primary care – specialist haematology advice is required.

 Results of serum protein electrophoresis AND urinary BJP suggest myeloma

Radiology reported as suggestive of myeloma and myeloma screen confirms myeloma.

When considering referral, take into account other features including:

• hypercalcaemia
• abnormal FBC
• acute kidney injury

Myeloma is unlikely with a IgG<15g/l or IgA<10g/l in the absence of other symptoms (e.g. renal failure, hypercalcaemia, back pain, bone marrow failure) in which case consider a routine referral.

A polyclonal (diffuse increase in gammaglobulin is not associated with haematological malignancy

2WW Haematology Services are available at Weston (WAHT), Bristol Haematology & Oncology Centre (UHB) and Southmead (NBT)

 A combination of symptoms and laboratory results can be used to determine the probability of myeloma being present.

Outpatient referral to haematologist advised if paraproteinaemia and one or more of the following:

• IgD or IgE paraproteins irrespective of concentration
• IgG paraproteins >15 g/l
• IgA or IgM paraproteins >10 g/l
• significant Bence Jones proteinuria (>500mg/l)
• unexplained immune paresis (low serum immunoglobulins) in absence of paraproteinaemia
• unexplained anaemia
• unexplained stable renal impairment
• mild hypercalcaemia (2.6 to 2.8 mmol/l)
• unexpected osteoporosis or fragility fracture (i.e. younger age group)

Local administrative information

 The standard RSS referral form is available as an EMIS template

 Immediate referral to hospital is necessary if any of the following are present:

• suspected spinal cord compression
• unexplained hypercalcaemia >2.8 mmol/l
• unexplained new onset renal failure

 2WW referral criteria

Results of serum protein electrophoresis AND urinary BJP suggest myeloma

Radiology reported as suggestive of myeloma and myeloma screen confirms myeloma.

2WW Haematology Services are available at Weston (WAHT), Bristol Haematology & Oncology Centre (UHB) and Southmead (NBT)

  2WW referral forms are available as EMIS templates

 
Spinal cord compression or acute kidney injury suspected of being caused by myeloma should be discussed more urgently with on call haematologist

 Discuss urgently with on call haematologist