Multiple myeloma (MM) is a haematological malignancy characterised by plasma cell proliferation. It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells. MM is the second most common haematological malignancy.


  • Incidence: 10.00 cases per 100,000 person-years
  • Peak incidence: 60-70 years
  • Sex ratio: more common in males 1.3:1
Condition Relative
Myelodysplastic syndrome0.30
Waldenstrom's macroglobulinaemia0.06
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+


Hypercalcaemia in myeloma
  • primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
  • much less common contributing factors: impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels

Clinical features

Use the pneumonic CRABBI:
  • Calcium: Hypercalcaemia occurs as a result of increased osteoclast activity within the bones. This leads to constipation, nausea, anorexia and confusion
  • Renal: Monoclonal production of immunoglobulins results in light chain deposition within the renal tubules. This causes renal damage which presents as dehydration and increasing thirst
  • Anaemia: Bone marrow crowding suppresses erythropoiesis leading to anaemia. This causes fatigue and pallor
  • Bleeding: bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
  • Bones: Bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions. This may present as pain (especially in the back) and increases the risk of fragility fractures
  • Infection: a reduction in the production of normal immunoglobulins results in increased susceptibility to infection

Referral criteria

NICE cancer referral guidelines for cancer suggest the following:

Offer a full blood count, blood tests for calcium and plasma viscosity or erythrocyte sedimentation rate to assess for myeloma in people aged 60 and over with persistent bone pain, particularly back pain, or unexplained fracture.

Offer very urgent protein electrophoresis and a Bence‑Jones protein urine test (within 48 hours) to assess for myeloma in people aged 60 and over with hypercalcaemia or leukopenia and a presentation that is consistent with possible myeloma.

Consider very urgent protein electrophoresis and a Bence‑Jones protein urine test (within 48 hours) to assess for myeloma if the plasma viscosity or erythrocyte sedimentation rate and presentation are consistent with possible myeloma.

Refer people using a suspected cancer pathway referral (for an appointment within 2 weeks) if the results of protein electrophoresis or a Bence‑Jones protein urine test suggest myeloma.


  • bloods may show anaemia (FBC) and thrombocytopenia (FBC); raised urea and creatinine (U&E) and raised calcium
  • monoclonal proteins (usually IgG or IgA) in the serum and urine (Bence Jones proteins)
  • bone marrow aspiration and trephine biopsy: confirms the diagnosis if the number of plasma cells is significantly raised
  • historically a skeletal survey has been done to look for bone lesions. However, whole-body MRI is increasingly used and is now recommended in the 2016 NICE guidelines
  • X-rays: 'rain-drop skull' (likened to the pattern rain forms after hitting a surface and splashing, where it leaves a random pattern of dark spots). Note that a very similar, but subtly different finding is found in primary hyperparathyroidism - 'pepperpot skull'


It is important to accurately diagnose multiple myeloma, as unlike its pre-malignant counterparts (Monoclonal gammopathy of undetermined significance and Smoldering myeloma), treatment must begin immediately due to the risk of complications occurring as a result on end-organ damage.
Symptomatic multiple myeloma is defined at diagnosis by the presence of the following three factors:
  • Monoclonal plasma cells in the bone marrow >10%
  • Monoclonal protein within the serum or the urine (as determined by electrophoresis)
  • Evidence of end-organ damage e.g. hypercalcaemia, elevated creatinine, anaemia or lytic bone lesions/fractures


Myeloma is a chronic relapsing and remitting malignancy which is currently deemed incurable. Management aims to control symptoms, reduce complications and prolong survival.

For those who have just been diagnosed with symptomatic multiple myeloma, treatment begins with induction therapy:
  • For patients who are suitable for autologous stem cell transplantation* induction therapy consists of Bortezomib + Dexamethasone
  • For patients who are unsuitable for autologous stem cell transplantation*, induction therapy consists of Thalidomide + an Alkylating agent + Dexamethasone

Typically it is younger, healthier patients who are suitable for stem cell transplantation and rigorous chemotherapy regimes.

After completion of treatment, patients are monitored every 3 months with blood tests and electrophoresis. Many will achieve remission and will not need further therapy for some time.

Many patients do relapse after initial therapy. If this occurs the 1st line recommended treatment is Bortezomib monotherapy. Some patients may also be suitable for a repeat autologous stem cell transplant, but this is decided on a case-by-case basis.

*An autologous stem cell transplant is used after high dose chemotherapy administration which targets stem cells. It involves the removal of a patient's own stem cells prior to chemotherapy, which are then replaced after chemotherapy. This is different from Allogenic stem cell transplantation where stem cells are sourced from HLA matching donors. Allogenic stem cell transplantation is currently only used as part of clinical trials when treating multiple myeloma.


A large part of multiple myeloma treatment involves managing complications:
  • Pain: treat with analgesia (using the WHO analgesic ladder)
  • Pathological fracture: Zoledronic acid is given to prevent and manage osteoporosis and fragility fractures as these are a large cause of morbidity and mortality, particularly in the elderly.
  • Infection: patients receive annual influenza vaccinations. They may also receive Immunoglobulin replacement therapy.
  • VTE prophylaxis
  • Fatigue: treat all possible underlying causes. If symptoms persist consider an erythropoietin analogue.


B2-microglobulin is a useful marker of prognosis - raised levels imply poor prognosis. Low levels of albumin are also associated with a poor prognosis

International prognostic index

StageCriteriaMedian survival (months)
IB2 microglobulin < 3.5 mg/l
Albumin > 35 g/l
IINot I or III45
IIIB2 microglobulin > 5.5 mg/l29