Multiple Myeloma

Question 1

What is the main Ig product?

Answer 1

IgG in two thirds

IgA in one third

Question 2

What is a specific marker of MM in the urine?

Answer 2

Bence Jones protein (in 2/3)

Question 3

Peak age of diagnosis? What population most common in?

Answer 3

70 years old

Twice as common in Afro Caribbeans as Caucasians

Question 4

Features of MM?

Answer 4

CRABBI

Hypercalcaemia
Eg abdominal pain, constipation, vomiting, reduced appetite, polyuria, polydipsia, confusion, depression, anorexia, fatigue, weakness, renal stones

Renal impairment
Presents as dehydration and thirst

Anaemia
Presents as fatigue and pallor

Bleeding
Increased risk of bleeding and bruising

Bones
Lyric bone lesions and osteoporosis
Presents with back pain, pathological fractures and vertebral collapse

(Do serum electrophoresis on all over 50s with back pain)

Infection
Immunoparesis - Reduced production of normal immunoglobulins
Neutropenia - disease and chemotherapy
Recurrent bacteria, infections

Question 5

Patients with MM can often get features of amyloidosis. What are these?

Answer 5

Macro gloss is
Carpal tunnel syndrome 
Neuropathy
Hyperviscosity 
Subcutaneous nodules
Swelling of shoulder joints

Question 6

What investigations do for MM?

Answer 6

FBC = normochromic normocytic anaemia, thrombocytopenia, leucopenia

U&Es = raised urea and creatinine

Persistently raised ESR, raised calcium with suppressed PTH, ALP usually normal

Blood film : rouleaux formation

Bone marrow aspiration and trephine biopsy (most accurate- confirms diagnosis if number of plasma cells significantly raised and in abnormal form)

Serum and urine protein electrophoresis
Raised conc of monoclonal IgG or IgA in serum, Bence Jones protein in urine

Imaging
X-RAYS
- rain drop skull due to lytic lesions
-vertebral collapse or osteoporosis

Whole body MRI to detect lesions not seen on XR

Question 7

How diagnose MM?

Answer 7

SYMPTOMATIC MM defined at diagnosis by presence of following factors:

1. Monoclonal plasma cells in bone marrow >10%
2. Monoclonal protein band within serum or urine as determined by electrophoresis
3. Evidence of end stage organ damage eg anaemia, hypercalcaemia, renal insufficiency
4. Lytic bone lesions

Question 8

What is the supportive management for MM?

Answer 8

Renal insufficiency management:

• rehydrate and ensure adequate fluid intake of 3L/day
• dialysis may be needed in AKI

Anaemia management:

• Transfusions
• EPO

Bone management:

• bisphosphonates
• analgesia to manage pain
• orthopaedic procedures eg vertebroplasty or kyphoplasty

Infection management:

• Broad spectrum antibiotics until cultures known
• regular IV Immunoglobulin infusions if recurrent

VTE PROPHYLAXIS

Local radiotherapy can help rapidly in focal disease

Question 9

How are chemotherapy and stem cell transplantation used in MM treatment?

Answer 9

Treatment begins with induction therapy of chemo

Patients suitable for autologous stem cell transplantation:
Bortezomib/ lenalidomide and dexamethasone
Autologous stem cell transplantation then follows

Patients unsuitable for autologous stem cell transplantation:
Thalidomide and alkylation agent eg cyclophosphamide and dexamethasone
This induction therapy for those unsuitable continues for 12-18 months or until serum paraprotein levels plateau
Treatment then held until paraprotein levels inevitably start to rise again where further chemotherapy / stem cell transplantation may be considered

After treatment, monitor pt every 3 months with blood tests and electrophoresis for signs or relapse (bortezomib 1st line if this occurs, some patients may be eligible for transplant)

Question 10

Side effects of lenalidomide?

Answer 10

Teratogenic immunomodulator with notable side effects of:

Neutropenia and thromboembolism

Question 11

What are the complications of MM?

Answer 11

Hypercalcaemia
Rehydrate vigorously with IV saline 0.9% 4-6 L/d
IV bisohosphonates useful for treating acute hypercalcaemia

Spinal cord compression
Urgent MRI needed treat with dexamethosome and local radiotherapy

Hyperviscosity
Caused reduced cognition, blurred vision and bleeding
Treat with plasmapheresis

Acute renal injury
Treat with rehydration
Dialysis may be needed

Question 12

What are the markers of poor prognosis in MM?

Answer 12

Greater than 2 osteolytic lesions
B2 microglobulin >5.5 mg/l
Hb < 11 g/l
Albumin < 30g/l