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 CME MEDICAL
ORIGINAL MASTERCLASS
RESEARCH Clinical Medicine
Clinical 2019
Medicine Vol Vol
2017 19, 17,
No No
1: 58–60
6: 58–8

Haematology: multiple myeloma

Authors: Medical Masterclass contributors; edited by John FirthA

Aetiology/pathophysiology
Multiple myeloma (MM) is characterised by the accumulation of
clonal, malignant plasma cells in the bone marrow. The cause of
myeloma is unknown. Radiation may be a factor in some cases
(although there is no association with therapeutic radiation). Exposure
to industrial/agricultural toxins or viruses have all been considered, but
proof is lacking. Chromosomal abnormalities have been identified,
most commonly involving the immunoglobulin heavy chain switch
region (on the long arm of chromosome 14), although these do not
appear to be enough on their own to give rise to MM. The tumour
cells within the bone marrow are supported by a non-malignant
population of stromal cells that produce cytokines (eg interleukin-6)
that enhance myeloma cell growth and prevent apoptosis.

Epidemiology Fig 1. Myeloma cells. This bone marrow shows a number of different types of
cell. The larger cells with eccentric nuclei and basophilic cytoplasm are myeloma
MM accounts for about 10% of haematological malignancies. cells. Note the perinuclear transparency that represents the Golgi apparatus.
The annual incidence in the UK is 5 per 100,000. Black people are
affected twice as commonly as white people, and males more than
females. The median age for diagnosis is 65 years, with fewer than
3% of patients presenting when they are younger than 40 years. > Erythrocyte sedimentation rate (ESR) is raised (the positive
charge of the protein neutralises the negative charge of sialic acid
Clinical presentation on the erythrocyte membrane, reducing their natural tendency to
repulse each other and causing the cells to fall faster in a column).
Common
> Biochemistry can show raised calcium (usually with a normal
> bone pain and pathological fractures alkaline phosphatase) and renal impairment.
> anaemia (bone marrow failure) > Serum electrophoresis may demonstrate a monoclonal protein.
> recurrent infections (due to immunoparesis) This is an immunoglobulin (Ig)G or IgA in most cases, but can be
> hypercalcaemia any class of Ig. Reduced levels of normal immunoglobulins are
> renal failure (multiple aetiologies: hypercalcaemia, light chain supportive.
deposition, non-steroidal drugs, anaemia, infections) > Excess serum free light chains, either kappa or lambda, may be
> abnormal bleeding (due to platelet dysfunction) demonstrated in the serum (sometimes the plasma cell clone is
making only light chains).
Rare > The diagnosis of myeloma depends on demonstrating increased
plasma cells (>10%) in the bone marrow (Fig 1).
> hyperviscosity syndrome (ischaemia, heart failure and
> Skeletal survey X-rays may demonstrate lytic lesions (Fig 2).
neurological problems)
> amyloid disease (eg carpal tunnel syndrome)
Staging (the International Staging System)
Investigations Staging (the International Staging System (ISS)) relates to levels of
albumin and the protein β2-microglobulin (Table 1).
If myeloma is suspected, the following tests may be useful.
> FBC can reveal normochromic, normocytic anaemia. Table 1. Staging of myeloma (ISS).
Stage 1 Stage 2 Stage 3

A
β2-microglobulin Neither 1 nor 3 β2-microglobulin >5.5 g/dL
Extract from Medical Masterclass (third edition, 2018) produced <3.5 mg/dL
by the Royal College of Physicians and written by over 75 authors
and contributors, under the editor-in-chief Dr John Firth Albumin >35 g/L

58 © Royal College of Physicians 2019. All rights reserved.

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Chemotherapy
Chemotherapy treatment, in combination with steroids, is the
mainstay of treatment in newly diagnosed patients. Many
new treatments have been developed in the past 10–15 years
including thalidomide and lenalidomide (the mechanism
of action of which is still under investigation but possibly
anti-angiogeneic) and bortezomib (a proteasome inhibitor).
Toxicities of these drugs include thromboembolic events and
peripheral neuropathy. These regimens can be given as pulsed
therapy (ie repeated at regular time intervals), either orally or
as subcutaneous injections. The response rates are high: some
patients enter complete remission, but most enter a ‘plateau
phase’ with a lower but steady paraprotein. All patients will
eventually relapse. More intensive regimens are used in younger
and fitter patients, and these can be used to debulk disease prior
to transplantation.

Autologous stem-cell transplantation

Fig 2. Myeloma of bone. Note that the symphysis pubis has been eroded The safety of these procedures now means that they have become
by myeloma. There are no apparent deposits in the upper femurs or pelvis. applicable to a larger number of patients. Many haematologists
would consider patients up to the age of 70 as eligible for
autologous transplants as part of their first line of treatment (ie
debulk with chemotherapy first, but proceed directly to transplant
thereafter). This depends on the overall condition of the patient
Differential diagnosis of a serum paraprotein and their response to chemotherapy. Second autologous
Malignant transplants may also be performed, often with good results.

> Waldenström’s macroglobulinaemia

> lymphoma
Allogeneic stem-cell transplantation
> chronic lymphocytic leukaemia This is only an option for a minority of patients, particularly those
> primary amyloidosis who are young, fit and have a human leukocyte antigen-matched
> plasma cell leukaemia sibling (or well-matched unrelated) donor. Response rates are high,
but unfortunately relapse is common.
Benign/stable
> monoclonal gammopathy of uncertain significance Maintenance therapy
> AIDS Lenalidomide is used as maintenance therapy after
relapse, to help prolong remission. Toxicities include venous
Treatment thromboembolism (so anticoagulation is often prescribed to
prevent this), cramp and cytopenias.
Myeloma may present as an acute emergency:
> acute kidney injury: prompt treatment of volume depletion is
Plasmapheresis
critical; involve the nephrologists early
> hypercalcaemia: fluids and bisphosphonates are critical Plasma viscosity may provide an indication for plasmapheresis
> spinal cord compression: a radiotherapy emergency but clinical features are far more important. Evidence of critical
> hyperviscosity: consider plasmapheresis. ischaemia, neurological syndrome or coma may improve following
this intervention.
Specific treatment depends on a number of factors such as
comorbidities and the presence of poor prognostic factors (see
Supportive care
below). There is no known cure for myeloma, but in recent years
the treatments for it have improved dramatically. Many patients Hypercalcaemia should be managed with fluids and
may now achieve a stable remission, lasting a number of years, bisphosphonates initially. Bisphosphonates should be continued
through a combination of chemotherapy and autologous stem-cell on a monthly basis, even with a normal calcium level, as there is a
transplantation. suggestion that they may reduce bony disease and modulate
Most haematologists will participate in trials, ensuring standard the disorder.
treatment for patients and access to drugs which may be Pain is common in myeloma and often requires opiate analgesia
otherwise unavailable (ie are funded for patients who are on plus NSAIDs. Radiotherapy may be helpful in controlling pain due
trials). to localised bony lesions.

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Recurrent blood transfusions and antibiotics may be required as particularly when first explaining the situation. Societies exist for
a result of both the disease and the treatment. In patients who support and information, and the patient should be given access
have recurrent infections, prophylactic infusions of intravenous to these.
immunoglobulins may be considered.
Prognosis
Psychological support Median survival with chemotherapy is about 3–5 years. A high ISS
The patient will almost certainly need some help in coming stage (see above) correlates with a poor prognosis. ■
to terms with the diagnosis. Try to involve family or friends,

60 © Royal College of Physicians 2019. All rights reserved.

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