11/14/24, 10\:55 AM Multiple Myeloma

Multiple Myeloma

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Multiple myeloma\: malignancy of plasma cells causing overproduction of monoclonal immunoglobulins; leads to anaemia,
immune impairment, and renal damage.
Types\: IgG (2/3 cases), IgA (1/3 cases), IgD/IgM (rare).
CRAB features\: hypercalcaemia, renal failure, anaemia, bone lesions.
Investigations\: FBC (anaemia, thrombocytopaenia), U&Es (raised creatinine), bone pro
blood
Management\: stem cell transplant (autologous/allogeneic), chemotherapy (if transplant unsuitable), maintenance
chemotherapy, treatment rotation upon relapse.
Complications\: pathological fractures, recurrent infections (respiratory, urinary), amyloidosis, spinal cord compression.
Prognosis\: median survival 4.5 years with stem cell transplant; 5-year survival ~55%.
Relapse/resistance\: re-treatment with original or new agents, potential second transplant, resistance develops over time.
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A comprehensive topic overview

Introduction

Multiple myeloma is a disease of plasma cells (antibody-producing B lymphocytes). Normally, a large variety of plasma
cells produce various forms of immunoglobulin. In myeloma, one particular plasma cell clone begins to replicate
uncontrollably, resulting in massive overproduction of one type of immunoglobulin. This spike in a speci
immunoglobulin can be seen as a monoclonal band on serum and urine electrophoresis.
These plasma cell clones accumulate in the bone marrow, crowding out the normal healthy tissue responsible for
producing normal blood cells. This prevents the production of normal levels of healthy blood cells, resulting in issues such
as anaemia, impaired immune function, and low platelets.
The abnormal plasma cells also produce a paraprotein. These paraproteins are abnormal immunoglobulin light chains that
can damage the kidneys by forming protein casts in the renal tubules. The abnormal plasma cells also secrete factors that
activate osteoclasts to break down bone, resulting in widespread lytic lesions, bone pain, and hypercalcaemia.

Types of myeloma

Myeloma is classi
IgG\: approximately 2/3 of cases
IgA\: approximately 1/3 of cases
IgD and IgM\: rare

Clinical features

CRAB is a useful mnemonic to help remember the most common features of myeloma\:¹
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HyperCalcaemia
Renal failure
Anaemia
Bone lesions
Bone pain
Bone pain is the most common symptom of myeloma, with 70% of patients a
spine and ribs, which typically worsens with activity.
Pain occurs due to increased osteoclast activity within the bones, which creates lytic lesions. Persistent pain in a particular
area should raise suspicion of a pathological fracture. Due to the resorption of bone, hypercalcaemia also develops.
Renal failure
Renal failure occurs primarily due to the tubulopathic e
nephrocalcinosis, further contributing to renal failure.
Direct invasion of renal tissue by plasma cells is rare, however, can sometimes occur. Amyloidosis can also contribute to
renal failure but to a small degree.
Recurrent urinary tract infections secondary to reduced immune function can worsen renal function.
Common symptoms
Nausea, vomiting, weight loss and lethargy\: due to uraemia
Pruritis and muscle cramping\: due to hyperphosphataemia
Shortness of breath and oedema\: due to pulmonary oedema secondary poor
Anaemia and thrombocytopaenia
Plasma cells invading the bone marrow inhibit the production of red cells and platelets, resulting in anaemia and
thrombocytopenia.
Anaemia
haemoglobin level.
Symptoms include shortness of breath and fatigue. Repeated transfusions are often required to maintain an adequate
Thrombocytopenia
9
This is often asymptomatic, but if platelets reach critically low levels (\<10 x 10 /L), symptoms such as petechiae, bruising
and bleeding develop. Patients often require monitoring of platelets and repeated platelet transfusions.
Infection
Due to the diseased plasma cells, patients have abnormally high levels of immunoglobulin. However, despite this, the
immunoglobulin is mutated, faulty, and ine
patients are signi
The most common infections are respiratory and urinary. Patients are more susceptible to viral infections, which must be
recognised and treated quickly, as they can often rapidly progress.
Some patients with particularly low levels of immunoglobulins can have intravenous immunoglobulin replacement.
Common symptoms
Fevers
Rigors
Productive cough
Dysuria
Rash
Headache
Neurological symptoms
Neurological syndromes are typically caused by the complications of myeloma and include\:
Confusion, weakness and fatigue\: hypercalcaemia
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Headaches and visual disturbances\: hyperviscosity (present in some paraproteinaemia)
Peripheral neuropathy\: amyloid deposition
Limb weakness and loss of bowel/bladder control\: spinal cord compression

Investigations

Laboratory investigations
Typical laboratory investigations include\:
Full blood count\: may show anaemia (normocytic and normochromic), neutropaenia and thrombocytopaenia
Urea and electrolytes\: may show raised creatinine and renal impairment
Bone pro\: may show hypercalcaemia and hyperphosphataemia
Erythrocyte sedimentation rate (ESR)\: persistently raised
Blood
Special laboratory investigations include\:
Immunoglobulins\: measurement of IgG/IgM/IgA to identify immune paresis
Serum and urine protein electrophoresis (Bence Jones protein)\: may show monoclonal bands or raised free light chains
Serum free light chains\: for assessing response to treatment and identifying relapse
Imaging
Whole body MRI\: most sensitive at detecting lytic lesions
Skeletal survey\: series of X-rays of the skull, axial skeleton and proximal long bones for lytic lesions
Bone marrow biopsy
Performed to assess the percentage of bone marrow occupied by plasma cells, which aids diagnostic strati
Immunohistochemistry is used to identify plasma cells. Cytogenetics can also be performed to assess for particular
mutations and translocations, which can guide treatment.

Diagnosis

The International Myeloma Working Group developed criteria for the diagnosis of myeloma.
¹ The criteria separate three
distinct diagnoses within the myeloma spectrum of disease\:
Symptomatic myeloma
Asymptomatic myeloma
Monoclonal gammopathy of undetermined signi
Symptomatic myeloma
The diagnostic criteria for symptomatic myeloma include\:
Clonal plasma cells >10% on bone marrow biopsy or in a biopsy from other tissues
A monoclonal protein (paraprotein) in either serum or urine
Evidence of end-organ damage related to the plasma cell disorder
Active treatment is considered for most patients who can tolerate it.
Asymptomatic myeloma
This is often called smouldering myeloma and is di
damage.
Often, these patients do not receive treatment initially, and a watch-and-wait approach is adopted, with regular reviews in
a haematology clinic.
If patients begin to develop end-organ damage, treatment is considered.
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The diagnostic criteria for asymptomatic myeloma include\:
Serum paraprotein >30 g/L
+/- clonal plasma cells >10% on bone marrow biopsy
No myeloma-related organ or tissue impairment
Monoclonal gammopathy of undetermined signi
Monoclonal gammopathy of undetermined signi
presence of elevated serum paraproteins but at a lesser level than actual myeloma (\<30 g/L).
The bone marrow has a smaller number of clonal plasma cells within it, and there is no end-organ damage.
MGUS usually requires no treatment but does require monitoring as it can evolve into myeloma (about 1-2% per year).
The diagnostic criteria for MGUS include\:
Serum paraprotein \<30 g/L
Clonal plasma cells \<10% on bone marrow biopsy
No myeloma-related organ or tissue impairment

Management

The overall goal of management in multiple myeloma is to reduce the disease-causing plasma cell population, therefore
reducing symptoms and signs of disease.
Initial therapy
Stem cell transplantation
Autologous hematopoietic stem cell transplantation involves extracting a patient's stem cells, followed by an initial
course of induction chemotherapy. The extracted stem cells are then reintroduced post-chemotherapy.
A small number of patients receive allogeneic stem cell transplantation. 3
This involves the transplantation of another
healthy individual's stem cells into the patient and o
greater mortality rate (5-10%).
3
Chemotherapy alone
For patients >65 years old with signi
common treatment regimes involve chemotherapy alone.
Maintenance
This involves regular chemotherapy, which has been shown to increase progression-free survival.
The decisions regarding maintenance therapy are tailored to each patient and treatments may be rotated if one becomes
ine
Patients are regularly reviewed, and blood tests monitored to assess disease response.
Relapse
Although myeloma is often treatable, it is di
If relapse occurs, the patient may undergo re-treatment with the original agent they previously received. Alternatively, they
may be treated with another chemotherapy agent.
Some relatively healthy patients may undergo a second autologous stem cell transplant.
Resistance
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As the disease progresses, treatment resistance can develop, rendering previously e
circumstance, a change to another agent is tried to see if adequate disease control can be achieved. Sometimes,
switching to a new agent can cause the patient to become re-sensitised to the original treatment.

Prognosis

With high-dose chemotherapy followed by autologous stem cell transplantation, the median survival has been estimated
to be 4.5 years. The overall 5-year survival rate is around 55%.
5

References

International Myeloma Working Group (2003).
"Criteria for the classi
myeloma and related disorders\: a report of the International Myeloma Working Group"
. Br. J. Haematol. 121 (5)\: 749–57
Kyle, R.A., Rajkumar, S.V. (2008).
"Multiple myeloma"
. Blood. 111 (6)\: 2962–72.doi\:10.1182/blood-2007-10-
078022. PMC 2265446. PMID 18332230.
Kyle RA, Rajkumar SV (2004).
"Multiple myeloma"
. N. Engl. J. Med. 351 (18)\: 1860–
73. doi\:10.1056/NEJMra041875. PMID 15509819.
San Miguel, J.F. et al. (2008).
J. Med. 359 (9)\: 906–917.
"Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma"
. N. Engl.
Cancer Research UK. Survival for myeloma. 2023. Available from\: [LINK].

Acute Myeloid Leukaemia
Anaemia Overview
Chronic Myeloid Leukaemia
Disseminated Intravascular Coagulation (DIC)
Haemolytic anaemia

Multiple Myeloma

Introduction

Types of myeloma

Clinical features

Investigations

Diagnosis

Management

Prognosis

References

Test yourself

Contents

Multiple Myeloma

Introduction

Types of myeloma

Clinical features

Investigations

Diagnosis

Management

Prognosis

References

Related notes

Test yourself

Contents