Clinical Review: Multiple myeloma

Multiple myeloma is a cancer of plasma cells, a type of white blood cell normally responsible for producing antibodies

The MRI scan showed infilrated lesion involving T3 and T4

Section 1: Epidemiology and aetiology

Myeloma is a rare, genetically heterogeneous, haematological malignancy of plasma cells, accounting for approximately 50 cases per million per year in the UK.1

The median age at presentation is 70 years, although a small number of patients may present before 50 years of age.

A defining feature in most cases is the presence of an abnormal monoclonal immunoglobulin (paraprotein or M-protein). About 20% of cases have only light chains (Bence Jones myeloma) and about 5% have no detectable paraprotein (non-secretory myeloma). Myeloma is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS).2

In unselected populations, the incidence of MGUS is about 1%, increasing with age to about 3% of those aged over 70. Progression from MGUS to myeloma or a related condition occurs at about 1% per year.

The only unequivocal risk factors for myeloma are male sex, older age and black ethnicity.3 The ethnic variation suggests a genetic underpinning to myeloma risk.

Myeloma/MGUS incidence is also two to three times higher in first-degree relatives of patients with myeloma/MGUS.4 Susceptibility genes have been identified, but the low associated risk does not justify population or familial screening.5,6 Immunosuppression is associated with a threefold increase in myeloma incidence. Tobacco, alcohol and chemical exposure do not appear to be risk factors for myeloma. There is weak evidence that ionising radiation may be myelomagenic.

The key classification is for MGUS, asymptomatic (smouldering) and symptomatic myeloma (see table 1).

Section 2: Making the diagnosis

Myeloma often presents insidiously with symptoms such as fatigue, bone pain and recurrent infections. Clinical features include symptoms of:

  • Bone disease (80-90%)
  • Impaired renal function (20-30%)
  • Anaemia ((approx)80%)
  • Hypercalcaemia
  • Recurrent or persistent bacterial infection
  • Hyperviscosity

Patients with suspected myeloma require urgent referral. Spinal cord compression, hypercalcaemia and renal failure are medical emergencies.7 Guidelines have been published for investigation of asymptomatic patients with a paraprotein.2

Back pain is very common, but the red flags approach can be used to identify patients who require further investigation (see box 1).8,9


To screen patients with possible myeloma, the following are required:7


Normocytic normochromic anaemia (typically Hb 90-100g/L) is usually present, but Hb may be normal in asymptomatic myeloma.

ESR is typically markedly raised (often >100mm/h), but may be normal in non-secretory or light chain only patients.

Renal function: May be normal; urea and creatinine may indicate renal damage, requiring immediate withdrawal of nephrotoxic drugs, referral for admission/rehydration and treatment of associated hypercalcaemia.

Calcium and albumin: Hypercalcaemia is found in 30% of patients at diagnosis.

Serum Ig levels: Typically globally reduced in myeloma (immune paresis), except for affected immunoglobulin subtype.

Serum/urine electrophoresis/free light chain assay: To check for paraprotein or free light chains in blood or urine (dipstick does not detect light chains).

Imaging of symptomatic areas: Plain X-ray or MRI (not bone scintigraphy). A negative X-ray alone does not exclude myeloma. Scintigraphy is not useful because osteoblast activity is suppressed in myeloma. Triage using the back pain red flags may assist in selecting patients for cross-sectional imaging such as CT or MRI.

Diagnosis: Patients with myeloma have the longest interval from first presented symptom to diagnosis;10,11 37% are emergency presentations, with poorer one-year survival.12

Symptomatic myeloma is defined by the presence of CRAB features (see table 1).

GPs can aid early diagnosis by:

  • Having a high index of suspicion
  • Prompt investigation of unexplained back pain
  • Urine and serum paraprotein and free light chain testing
  • Early referral (two-week wait rule)

Section 3: Managing the condition

The British Committee for Standards in Haematology has published guidelines on the management of myeloma7 (box 2) and supportive care for patients with the condition.13

Patients who are willing should be enrolled in a clinical trial if one is available. Myeloma UK ( has information about current trials.

Regardless of treatment offered, myeloma typically follows a relapsing, remitting course with a final refractory phase; the whole process can span 10 to 20 years and beyond.

Treatment of relapse depends on a number of factors, including age and fitness for SCT, duration of first remission and previous treatments.

If the first remission lasted a year or more, retreatment with the same or a similar regimen is likely to be effective.1

If relapse occurs in less than a year, or for a second or subsequent time, further agents may be added.

Primary refractory myeloma is rare but almost all patients will eventually develop refractory disease.

In this case, options include:

  • A different treatment with a different mode of action
  • Escalation of treatment as for early or repeated relapse
  • Clinical trial - if available, this may give access to new drugs
  • Supportive care - if the patient is unfit for, or does not wish to receive, aggressive therapy

Primary care support

  • Consider neutropenic sepsis in patients who are unwell on chemotherapy
  • Lower threshold for antibiotics in minor/moderate infections
  • If the patient develops new symptoms, consider relapse and refer to haematologist
  • Be aware of potential side-effects of treatment
  • Consider hyperviscosity syndrome if confusion, headaches or visual disturbance develop; fundoscopy may show tortuous, engorged retinal vessels
  • New back pain may indicate spinal cord compression - leg weakness and disturbance of bowel or bladder function
  • Liaise with the community symptom control team and hospital-based haematology team about minimising symptoms such as pain, constipation and fatigue
  • Avoid NSAIDs (renal risk)
  • Consider gabapentin or pregabalin for neuropathic pain

Section 4: Prognosis

Myeloma is treatable but is not considered curable, although some patients achieve long remission.

Median survival is now in the order of five years, with many patients surviving longer than 10 years.

Significant long-term complications include:

  • Skeletal deformity because of fractures, especially vertebral compression fractures
  • Peripheral neuropathy
  • Renal failure owing to light chain nephropathy, hypercalcaemia and certain drugs, such as NSAIDs
  • Venous thromboembolism
  • Amyloid light chain amyloidosis may complicate any plasma cell dyscrasia, causing, for example, cardiac or renal failure, postural dizziness or digestive complaints

If a patient develops new symptoms or exacerbation of existing ones, they should be reviewed for progression, relapse or complications. Prompt intervention is vital.

Section 5: Case study

A 47-year-old previously fit woman developed back and rib pain. There was no history of trauma, despite her hobby of horse riding.

She attended the GP practice on four occasions and was seen by different doctors each time. Various combinations of analgesia were prescribed, to no avail.

On the third visit, her chest X-ray was reported as normal. Owing to the persistent pain, she was referred to orthopaedics three months later and an outpatient MRI was requested.

The patient called her GP two weeks later complaining of 'wobbly legs' and was advised to await the MRI scan. She presented to A&E a month later with loss of power in the legs and loss of sensation.

An urgent MRI scan showed an infiltrative lesion involving T3 and T4 with soft tissue extension into the spinal canal, with cord compression at that level.

Blood tests showed marked anaemia with Hb 70g/L, abnormal renal function (creatinine 110 micromol/L) and hypercalcaemia (corrected calcium 2.7mmol/L). Her total IgA was elevated. She was referred urgently to a haematologist; her bone marrow biopsy showed sheets of plasma cells, confirming a diagnosis of myeloma, and she was admitted for steroids, IV fluids and a bisphosphonate infusion.

She underwent T3/4 decompression and laminectomy followed by radiotherapy and chemotherapy.

The patient achieved remission but remained on the rehabilitation unit for more than six months. Owing to her paraplegic state, her performance status was not good enough for SCT.

In the ensuing months, she regained sufficient power in her legs to be mobile with sticks and return to work, but she has never been able to return to horse riding.

Red flag features

A number of red flag features were present in this case, that could have led to a prompt diagnosis if blood tests were performed earlier.

A previously fit and active person under 50, who rarely visits the surgery, begins to make repeated attendances with escalating upper thoracic back pain.

The previous wellbeing and age of the patient are red flags, as is the location of the back pain.

Although the X-ray was reported as normal, the persistence and worsening of the pain is a trigger for cross-sectional imaging and referral. However, her call about having wobbly legs was not acted on, and the subsequent cord compression was not prevented.

Section 6: Evidence base

Clinical trials


  • 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). Br J Haematol 2009; 147: 22-42
  • British Committee for Standards in Haematology. Guidelines for the diagnosis and management of multiple myeloma. London, BCSH, 2013
  • Guidelines for supportive care in multiple myeloma 2011. Br J Haematol 2011; 154(1): 76-103


  • Schey SA, Yong KL, Marcus R et al (eds). Myeloma; Pathology, Diagnosis, and Treatment. Cambridge University Press, 2013

Online resources

Reflect on this article and add notes to your CPD organiser on MIMS Learning


1. Smith D, Yong K. BMJ 2013: 346: f3863.

2. Bird J, Behrens J, Westin J et al. Br J Haematol 2009: 147(1): 22-42.

3. Cancer Research UK. Myeloma Key Facts, in Cancer Statistics Key Facts. London, CRUK, 2014.

4. Greenberg AJ, Rajkumar SV, Vachon CM. Blood 2012; 119(23): 5359-66.

5. Weinhold N, Johnson DC, Rawstron AC et al. Blood 2014; 123(16): 2513-17.

6. Morgan GJ, Johnson DC, Weinhold N et al. Leukemia 2014; 28(3): 518-24.

7. Bird JM, Owen RG, D'Sa S et al. Guidelines for the diagnosis and management of multiple myeloma. London, British Committee for Standards in Haematology, 2013.

8. Greenwood J, Shipley M.

GPonline, 4 July 2014.

9. McCarthy CJ, Gittins M, Roberts C et al. Spine 2007; 32(8): 921-6.

10. Neal RD, Din NU, Hamilton W et al. Br J Cancer 2014; 110(3): 584-92.

11. Lyratzopoulos G, Neal RD, Barbiere JM et al. Lancet Oncol 2012; 13(4): 353-65.

12. Elliss-Brookes L, McPhail S, Ives A et al. Br J Cancer 2012; 107(8): 1220-6.

13. Snowden JA, Ahmedzai SH, Ashcroft J et al. Br J Haematol 2011; 154(1): 76-103.

14. Terpos E, Morgan G, Dimopoulos MA et al. J Clin Oncol 2013; 31(18): 2347-57.

  • Contributed by Dr Shirley D'Sa, consultant haematologist, WM, myeloma and POEMS clinics, University College London Hospitals NHS Foundation Trust and Mount Vernon Cancer Centre, London.

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Audit patients who have been diagnosed with multiple myeloma in the past five years. How did they present and what can be learned?
  • Ask your local consultant haematologist to give a talk about how GPs can improve their diagnostic skills in myeloma, including recognising the red flags.
  • Review the support your practice offers to patients with myeloma

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