Multiple Myeloma

Question 1

Define multiple myeloma

Answer 1

Malignancy of bone marrow plasma cells, the terminally differentiated and immunoglobulin (IgG or IgA) secreting cells

Question 2

What are the myeloma defining events

Answer 2

Bone marrow plasma cells >60%

Involved: uninvolved FLC ratio >100

> 1 focal lesion on MRI

Question 3

Describe the progression of myeloma

Answer 3

(1) MGUS – NO CRAB S/S
- Monoclonal serum protein < 30g/L
- BM plasma cells < 10%
- Annual risk of progression to MM 1-2%

(2) Smouldering myeloma – NO CRAB S/S
- Monoclonal serum protein ≥ 30g/L
- BM plasma cells ≥ 10%
- Annual risk of progression to MM 10%

(3) Multiple Myeloma – CRAB S/S

(4) B-cell leukaemia

Question 4

Aetiology and risk factor of multiple myeloma

Answer 4

Unknown. ? Viral trigger
Chromosomal aberrations: N-RAS, K-RAS, p16 methylation

RF:
Ionising radiation
Agricultural work
Occupational chemical exposures e.g. benzene
Family history of MM
MGUS

Question 5

Symptoms of multiple myeloma

Answer 5

Calcium high -> polyuria, polydipsia, constipation, mental status changes

Renal failure -> nephrotic syndrome, proteinuria, peripheral oedema

Anaemia -> SOB, fatigue,

Bone -> pain and osteoporosis fractures (hip, spine, wrist), vertebral collapse

Hyperviscosity -> headaches and visual disturbance

Question 6

Signs of multiple myeloma

Answer 6

General
- Anaemia: pallor
- Dehydration
- Purpura
- Macroglossia

Obs
- Tachycardia

Cardio
- Flow murmur
- Signs of heart failure

Abdo
- Hepatosplenomegaly

Neuro
- Carpal tunnel syndrome
- Peripheral neuropathies

Fundoscopy:
- Hyperviscosity → Retinal haemorrhages

Question 6

Criteria for multiple myeloma diagnosis

Answer 6

Must have a high index of suspicion (bone pain or back pain that does not improve)

1. Mononuclear protein band in serum or urine electrophoresis
2. Raised plasma cells on marrow biopsy
3. Evidence of end-organ damage from myeloma: Hypercalcaemia, renal insufficiency, anaemia
4. Bone lesions seen on skeletal survey

Question 7

Investigations for multiple myeloma

Answer 7

Urine: Bence Jones proteins

Serum electrophoresis: Serum paraprotein (2/3 IgG, 1/3 IgA) | Monoclonal protein band (single dense band)
Blood film: Rouleaux formation with blue background
FBC: Normocytic anaemia
ESR/CRP: raised
Renal: Cr raised
U+Es: Calcium raised
LFTs/ALP: NORMAL (differentiates from mets)
Free light chain assay: raised
Immunophenotyping: light chain restriction (either kappa or lambda)

Radiographs: osteolytic lesions without sclerosis (PUNCHED OUT), osteopenia
Bone marrow aspirate and trephine: raised plasma cells >10%

Question 8

Management for multiple myeloma

Answer 8

Steroids
Classical cytostatic drugs e.g. melphalan
Proteasome inhibitors
MoAbs (monoclonal antibodies) e.g. daratunumab
Immunomodulatory drugs (IMIDs) e.g. thalidomide, lenalidomide

+/- Abx prophylaxis

Question 9

Complications of multiple myeloma

Answer 9

Bone pain (Mx bisphosphonates)
Vertebral body fracture
Hypercalcaemia
Haem: anaemia, thrombocytopenia, leukopenia, Hyperviscosity
Neuropathies
Renal failure
Recurrent infection
Cardiac failure

Question 10

Prognosis for multiple myeloma

Answer 10

Incurable
Relapse 2-5 years after treatment is expected