Haematology 11 - Plasma cell myeloma and Monoclonal Gammopathy of Uncertain Significance

Question 1

What immunoglobin is produced by myeloma cells?

Answer 1

One single type (eith IgG or IgA) which is known as paraprotein or M spike

Question 2

What are Bence Jones proteins?

Answer 2

Urine monoclonal free light chains

Question 3

What is Waldenstrom’s-Lymphoplacytic lymphoma?

Answer 3

A lymphoplasmocytic lymphoma with IgM paraprotein that causes visual disturbances

Question 4

What is the name of the premalignant condition that always precedes myeloma?

Answer 4

Monoclonal gammaopathy of uncertain significance (MGUS)

Question 5

What are the two most significant risk factors for myeloma?

Answer 5

Obesity

Black > causasians/ asians

Question 6

What are the diagnostic criteria for MGUS?

Answer 6

Serum M-protein <30g/L
BM clonal plasma cells <10%
Asymptomatic

Question 7

What is smouldering myeloma?

Answer 7

Serum M-protein >30g/L
BM clonal plasma cells >10%
Asymptomatic

Question 8

What % of plasma cells is there in symptomatic multiple myeloma?

Answer 8

> 10%

Question 9

What is the most notable interaction of myeloma cells with the bone marrow micro-environment?

Answer 9

Produce RANK ligand which stimulates osteoclasts to cause bone resorptions

Question 10

What is the incidence of IgM myeloma?

Answer 10

Very rare (<1% of myelomas)

Question 11

What does CRAB stand for in myeloma diagnosis?

Answer 11

Calcium (hypercalcaemia, >2.75)

Renal (creatinine >177/ eGFR <40)

Anaemia

Bone disease (see lytic lesions)

Question 12

What is the most common and 2nd most common cytogenetic abnormality in myeloma?

Answer 12

1. Hyperdiploid karyotype

2. IgH gene rearrangement

Question 13

What are the 3 2014 Myeloma Defining Events

Answer 13

BM plasma cells >60%
involved:uninvolved FLC ratio >100
>1 focal lesion on MRI

Question 14

Which part of the skeleton is affected by myeloma?

Answer 14

Proximal skeleton (spine, skull, knees)

Question 15

Where are myeloma patients most likely to feel pain?

Answer 15

Back, chest wall, pelvis

Question 16

What % of myeloma patients present with bone disease?

Answer 16

80%

Question 17

What scan is necessary to detect bone lesions in myeloma?

Answer 17

Whole body CT is first line (X ray is obsolete for this use)
PET scan can also be used
Gold-standard = whole body diffusion-weighted MRI as this shows active vs treated disease

Question 18

What are the 2 most likely emergency presentations of myeloma?

Answer 18

Cord compression

Hypercalcaemia

Question 19

What tests should be done to diagnose myeloma?

Answer 19

First: 
Serum protein electrophoresis 
Serum free light chains 
Next: 
Bone marrow aspirate and biopsy for immunohistochemistry 
FISH (for prognostic)

Question 20

What is the best way to treat cord compression in myeloma?

Answer 20

Dexamethosone

Radiotherapy

Question 21

What risk does myeloma present to the kidney?

Answer 21

Cast nephropathy - FLCs and Bence Jones proteinuria cause proximal tubule cell injury

Question 22

How should myeloma kidney disease be treated in an emergency?

Answer 22

Bortezomib-based therapy is the cornerstone of myeloma kidney disease treatment - once the patients can become independent from dialysis their outcomes improve dramatically

Question 23

How does myeloma affect immunity?

Answer 23

Serum levels of normal Igs reduced

BM micro-environment interference also impairs myeloid, T and NK cells

Chemo also impairs immune response

Question 24

What is tested for in BM biopsy in suspected myeloma?

Answer 24

Immunohistochemistry for CD138 - specific for myeloma cells in BM

Question 25

What test can detect cytogenetic abnormalities of prognostic significance in myeloma?

Answer 25

FISH

Question 26

What are the 3 parameters in the international staging system for myeloma?

Answer 26

Serum beta microglobulin Cytogenetic risk LDH

Question 27

How does AL amyloidosis link to myeloma?

Answer 27

Misfolded FLCs aggregate into amyloid in target organs

Question 28

How does amyloidosis affect the kidney?

Answer 28

Nephrotic syndrome

Question 29

Give 5 features of the clinical presentation of AL amyloidodis?

Answer 29

``` Nephrotic syndrome Unexplained heart failure Sensory neuropathy Abnormal liver function tests Macroglossia ```

Question 30

What is MGRS?

Answer 30

Monoclonal gammaopathy of Renal significance

Question 31

How is MGRS defined?

Answer 31

1. One or more kidney lesions caused by mechanisms related to the produced monoclonal immunoglobulin (Ig) 2. The underlying B cell clone does not cause tumor complications or meet current hematological criteria for immediate specific therapy

Question 32

How do proteasome inhibitors work in multiple myeloma

Answer 32

Proteasomes are involved in removing misfolded proteins If you prevent this, the amount of misfolded protein produced in myeloma will overwhelm the cell and cause apoptosis

Question 33

Which monoclonal antibody is used in myeloma treatment?

Answer 33

Anti-CD38 (daratumumab)

Question 34

What is the difference between a pre-myeloma MGUS and pre-lymphoma MGUS?

Answer 34

Pre-myeloma: IgG/A-producing B cells | Pre-lymphoma: IgM-producing B cells

Question 35

What are the 3 risk factors for MGUS progression?

Answer 35

1. Non-IgG M spike 2. M spike >15g/L 3. Abnormal serum free light chain ratio

Question 36

What are the clinical effects of myeloma due to?

Answer 36

1. BM microenvironment interaction | 2. Circulating paraprotein

Question 37

What is the cause of dinovoangiogenesis in myeloma?

Answer 37

CD34 expression on myeloma cells promotes angiogenesis

Question 38

What type of nephropathy does myeloma cause?

Answer 38

Cast nephropathy

Question 39

What are the first investigations to be done in suspected myeloma?

Answer 39

Serum protein electrophoresis | Serum free light chains

Question 40

What condition can produce MGUS/ myelomas part of its progression?

Answer 40

AL amyloidosis

Question 41

Recall 6 options for myeloma therapy

Answer 41

1. Alkylators (eg cyclophosphamide) 2. Steroids (eg dex + pred) 3. Thalidomide 4. Cereblon-binding drugs 5. Proteosome inhibitors 6. Anti-CD38 (daratumumab)

Question 42

How do cereblon-binding drugs work?

Answer 42

Decrease levels of IRF4 --> decreased myc --> myeloma cell death