Multiple Myeloma

Question 1

what is the definition of multiple myeloma?

Answer 1

• Cancer of differentiated B lymphocytes known as PLASMA CELLS (produce antibodies)
• The accumulation of malignant plasma cells in the bone marrow leads to progressive bone marrow failure

Question 2

what is the epidemiology of multiple myeloma?

Answer 2

• Peak age is 70 yrs

- More common in AFRO-CARIBBEANS than caucasians

Question 3

what is the aetiology of multiple myeloma?

Answer 3

It’s not known exactly what causes multiple myeloma. However, there is a close link between multiple myeloma and a condition called monoclonal gammopathy of unknown significance (MGUS)

Question 4

what are the risk factors for multiple myeloma?

Answer 4

Age
Male
Black race

Question 5

what is the pathophysiology of multiple myeloma?

Answer 5

Normal plasma cells produce a wide range of immunoglobulins (antibodies) such as IgG,IgA,IgM & IgD
- However in myeloma the malignant plasma cells just produce an EXCESS of one type of immunoglobulin this is known as monoclonal paraprotein:
• IgG (55%)
• IgA (20%)
• Rarely IgM and IgD
- Other immunoglobulin levels are low resulting in immunoparesis resulting in increased susceptibility to infections
- Leads to bone disease, hypercalcaemia and renal failure

Question 6

what are the key presentations of multiple myeloma?

Answer 6

OLD CRAB:
• OLD age
• Calcium elevated
• Renal failure - nephrotic syndrome, since due to raised immunoglobulins which are proteins which precipitate (especially immunoglobulin light chains) and deposit in organs ESPECIALLY the kidneys - results in THIRST due to lack of water retention due to failure
• Anaemia - neutropenia or thrombocytopenia resulting in infection, bleeding and fatigue and pallor
• Bone lytic lesions - back pain: Caused by malignant plasma cells releasing factors which in turn result in:
- The activation of osteoclasts thus increasing bone turnover and resulting in bone breakdown and lytic lesions (RANK ligand and IL-3 result in osteoclast activation)
- The inhibition of osteoblasts thus decreasing new bone formation (HGF and Dkk-1 result in osteoblast inhibition

Question 7

what are the signs of multiple myeloma?

Answer 7

Elevated calcium
Renal failure
Anaemia

Question 8

what are the symptoms of multiple myeloma?

Answer 8

Thirst 
Fatigue 
Pallor 
Back pain 
Recurrent infections

Question 9

what are the first line investigations for multiple myeloma?

Answer 9

Blood - Normocytic normochromic anaemia
• Raised ESR
• Rouleaux formation on blood film

Question 10

what are the gold standard investigations for multiple myeloma?

Answer 10

U & E’s:
• High calcium
• High alkaline phosphatase, Bence-jones protein in urine
- PLAIN X-ray:
• Lytic ‘punched-out’ lesions: Pepper-pot skull, Vertebral collapse
• Fractures
• Osteoporosis
- Serum & urine electrophoresis:
• B2-microglobulin present and is prognostic
- Diagnosis requires:
• Monoclonal protein band in serum or urine
• Increased plasma cells on bone marrow biopsy
• Hypercalcaemia/Renal failure/Anaemia
• Bone lesions on skeletal survey

Question 11

what are the differential diagnoses for multiple myeloma?

Answer 11

Depression · Osteoarthritis · Diabetes mellitus · Polymyalgia rheumatica · Monoclonal gammopathy of unknown significance (MGUS)

Question 12

how is multiple myeloma managed?

Answer 12

Bone pain supported with analgesia, avoid NSAIDs due to risk of renal impairment
- Give all patients bisphosphonate e.g. ZOLENDRONATE as they reduce fracture rates and bone pain
- Anaemia should be corrected with transfusion of RBCs and erythropoietin can be used
- Rehydrate and ensure adequate fluid intake of 3L/day to prevent further renal damage e.g. by immunoglobulin light chains
- Renal dialysis to treat acute renal failure
- Treat infections with broad-spectrum antibiotics quickly
- Chemotherapy:
• CTD - CYCLOPHOSPHAMIDE, THALIDOMIDE and DEXAMETHSONE - max 8 cycles - for less fit people
• VAD - VINCRISTINE, ADRIAMYCIN and DEXAMETHASONE in fitter people - max 6 cycles
- Stem cell transplant

Question 13

how is multiple myeloma monitored?

Answer 13

Monitor people with smouldering myeloma every 3 months for the first 5 years, and then decide the frequency of further monitoring

Question 14

what are the complications of multiple myeloma?

Answer 14

Leads to bone disease, hypercalcaemia and renal failure

Question 15

what is the prognosis of multiple myeloma?

Answer 15

almost 85 out of every 100 (almost 85%) will survive their myeloma for a year or more after diagnosis
more than 50 out of every 100 (more than 50%) will survive their myeloma for 5 years or more after diagnosis
around 30 out of every 100 (around 30%) will survive their myeloma for 10 years or more after they are diagnosed