Multiple myeloma

Question 1

What is multiple myeloma?

Answer 1

Presence of too many plasma cells in the bone marrow

There is a proliferation of abnormal protein immunoglobulins called paraproteins

Question 2

Why is the presence of too many plasma cells in the bone marrow a problem?

Answer 2

Unable to make normal blood
- patients have symptoms of “bone marrow failure”
- tiredness, infections, bruising

Erodes the bones causing “lytic lesions”
- often called plasmacytomas

Plasma cells release antibody into the blood
- referred to as “paraprotein”

Question 3

What mnemonic can help you remember the signs of multiple myeloma?

Answer 3

CRAB

Calcium (high calcium)
Renal (kidney problems)
Anaemia (low haemoglobin)
Bones (holes and fractures)

Question 4

What are the risk factors for multiple myeloma?

Answer 4

Increasing age

Gender (more common in men)

Ethnicity (develops at a younger age in black people)

FHx

Obesity

MGUS

Autoimmune conditions

Question 5

What is MGUS?

Answer 5

Monoclonal gammopathy of uncertain significance

A pre-malignant stage to multiple myeloma

Question 6

What are the unfavourable prognostic signs for multiple myeloma?

Answer 6

Beta-2 microglobinaemia

Renal impairment

High plasma cell counts

Diffuse multiple bone lesions or fracture

Marked anaemia

Hypercalcaemia

Question 6

Sources

Answer 6

https://cks.nice.org.uk/topics/multiple-myeloma/diagnosis/differential-diagnosis/

Haematological Malignancies lecture 30.11.21

https://www.nice.org.uk/guidance/ng35/chapter/Recommendations#laboratory-investigations

Question 7

According to NICE guidelines what are the lab investigations to do for people with suspected myeloma?

Answer 7

Serum protein electrophoresis and serum-free light-chain assay - to confirm presence of paraprotein indicating possible myeloma or MGUS

If serum protein electrophoresis is abnormal = use serum immunofixation to confirm the presence of paraprotein indicating possible myeloma or MGUS

If using bone marrow aspirate and trephine biopsy use morphology to determine plasma cell % and flow cytometry to determine plasma cell phenotype

Question 8

According to NICE guidelines what are the lab investigations to do for prognostic information in people with multiple myeloma?

Answer 8

Fluorescence in-situ hybridisation (FISH) ON CD138-selected bone marrow plasma cells to identify the adverse risk abnormalities t(4;14), t(14;16), 1q gain, del(1p) and del(17p)(TP53 deletion)

Use these abnormalities alongside International Staging Systems scores to identify people with high-risk myeloma

Consider doing FISH on CD138‑selected bone marrow plasma cells to identify the adverse risk abnormality t(14;20), and the standard risk abnormalities t(11;14) and hyperdiploidy

Consider performing immunophenotyping of bone marrow to identify plasma cell phenotype, and to inform subsequent monitoring

Consider performing immunohistochemistry (including Ki‑67 staining and p53 expression) on the trephine biopsy to identify plasma cell phenotype and give an indication of cell proliferation, to provide further prognostic information

Perform serum‑free light‑chain assay and use serum‑free light‑chain ratio to assess prognosis

Question 9

According to the BSMS lecture, what investigations should you do in the myeloma work-up?

Answer 9

Bloods
- haem = anaemia, rouleaux, viscosity, ESR
- biochem = Us&Es, Ca2+, albumin, total protein, LDH, CRP, β2-M

Serum protein electrophoresis
- paraprotein (monoclonal M band)
- immunoglobulin levels low (immune paresis)

Serum free light chain assay
- abnormal κ/λ light chain ratio

Staging investigations

Question 10

What mnemonic can you use to remember multiple myeloma investigations?

Answer 10

B – Bence–Jones protein (request urine electrophoresis)
L – Serum‑free Light‑chain assay
I – Serum Immunoglobulins
P – Serum Protein electrophoresis