Myelomas

Question 1

What is myeloma?

Answer 1

Myelomais a cancer of a specific type of plasma cell where there is agenetic mutationcausing it to rapidly and uncontrollably multiply

These plasma cells produce one type ofantibody (immunoglobulin)

Question 2

What is the median age of diagnosis of myeloma?

Answer 2

65

Question 3

What are some risk factors for myeloma?

Answer 3

• Male sex
• Black African ethnicity
• Family history
• Obesity

Question 4

How are myelomas classified?

Answer 4

Based on the isotype of antibody produced

Question 5

What are some classes of myeloma?

Answer 5

• IgG
• IgD
• Bence-Jones myeloma
• Non-secretory myeloma
• IgA
• Biclonal
• IgE

Question 6

Describe the formation of myeloma

Answer 6

Myeloma follows the double hit hypothesis

Normal plasma cells will recieve a genetic hit, leading to MGUS (Monoclonal gammopathy of undetermined significance)

Another hit from external factors will lead to asymptomatic myeloma, which can progress into overtly malignant myeloma

Question 7

What does MGUS stand for?

Answer 7

Monoclonal gammopathy of undetermined significance

Question 8

What is MGUS?

Answer 8

MGUS is the premalignant form of myeloma

Question 9

What causes MGUS?

Answer 9

Genetic mutation

Question 10

How is MGUS diagnosed?

Answer 10

Small increase in paraprotein
Bone marrow plasma cells <10%
- Normal calcium
- Normal renal function
- Normal haemoglobin
- No lytic lesions
- No increase in infections

Question 11

How is MGUS managed?

Answer 11

Screening for myeloma progression

Question 12

How does myeloma affect the body?

Answer 12

Direct tumour cell effects
Paraprotein mediated effects

Question 13

What are some direct tumour cell defects of myeloma?

Answer 13

Bone lesions
Increased calcium
Bone pain
Marrow failure -> Anaemia

Question 14

What are some paraprotein mediated effects of myeloma?

Answer 14

• Renal failure
• Immune suppression
• Hyperviscosity
• Amyloid

Question 15

What are some possible complications of myeloma?

Answer 15

• Sepsis
• Hypercalcaemia and dehydration
• Hyperuricaemia
• Amyloid

Question 16

What are some baseline tests performed in suspected myeloma?

Answer 16

• Bloods - FBC, U+Es and creatinine, calcium, CRP, plasma viscosity
• Serumprotein electrophoresis - shows the type of paraprotein
• Plain x-ray of symptomatic areasW

Question 17

What are some diagnostic tests used after baseline testing in myeloma?

Answer 17

• Bone marrow aspirate and trephine biopsy, with plasma cell phenotyping
• Immunofixation of serum and urine to confirm and show the subtype of the paraprotein
• Skeletal survey (Whole-body MRI first line, whole body low dose CT can be used if MRI unsuitable)
• Other tests to estimate tumour burden and prognosis e.g. FISH, serum beta-2 microglobulin concentration

Question 18

What is the most common type of antibody found as a paraprotein?

Answer 18

IgG

Question 19

What is myeloma bone disease?

Answer 19

The disregulation of bone remodelling, leading to typical lytic lesions, usually seen in the spine, skull, long bones and ribs

Question 20

What causes myeloma bone disease?

Answer 20

Myeloma cells can bind to marrow stromal cells, which causes the release of IL-6

This can cause osteoclast activation and osteoblast suppression, leading to increased bone lysis and thus fractures

This causes a rise in Ca2+ levels in the blood

Soft tissue plasmacytomas also occur and they are the usual cause of spinal cord compression

IL-6 and TGFß can also stimulate further myeloma cell proliferation

Question 21

What is the usual management of myeloma bone disease?

Answer 21

Bisphisphonates

Question 22

How does renal disease occur in myeloma?

Answer 22

This occurs by reaction of excess light chains in the thick ascending limb of the loop of Henle with Tamm-Horsfall proteins, causing the production of a cast (Cast nephropathy)

Question 23

How can renal failure in myeloma be managed?

Answer 23

Damage may be reversible with prompt treatment with hydration, stopping nephrotoxic drugs and using drugs which switch off light chain production such as chemotherapy or steroids

Question 24

What is the purpose of treatment in myeloma?

Answer 24

Myeloma is currently seen as an incurable chronic disease

Treatment is therefore used to improve quality of life and prolong survival

Question 25

How is myeloma managed?

Answer 25

Symptom control
Haematopoietic stem cell transplantation or chemotherapy

Question 26

Describe the process of haematopoietic stem cell transplantation

Answer 26

1. Administer pre-treatment to release blood stem cells from the bone marrow
2. Collect blood stem cells
3. Freeze until required
4. Administer chemotherapy to remove or partially remove immune system
5. Return thawed blood stem cells by infusion into a vein
6. Provide supportive medical treatment for at leats 4 weeks

Question 27

What are some chemotherapy agents used in myeloma?

Answer 27

• Corticosteroids (E.g. dexamethasone)
• Bortezomib (Proteasome inhibitor)
• Lenalidomide (Thalidomide)
• Monocloncal antibodies (e.g. daratumumab)
• Alkylating agents (E.g. Cyclophosphomide, melphalan)

Question 28

What are some methods of symptom control in myeloma?

Answer 28

• Opiate analgesia (No NSAIDs due to kidney damage)
• Local radiotherapy
• Bisphosphonates
• Vertebroplasty (Inject sterile cement into fractures bone to stabilise)