Haematology 6 - Multiple myeloma, MGUS, amyloid

Question 1

In MM, what is the immunoglobulin class of the plasma cells?

Answer 1

IgG or IgA

Question 2

What does CRAB stand for?

Answer 2

Calcium (high)
Renal failure
Anaemia
Bone lesions (lytic)

Question 3

What is the precursor, pre-malignant condition of MM?

Answer 3

monoclonal gammopathy of undetermined significance (MGUS)

Question 4

How to differentiate between Waldenstrom’s and MM?

Answer 4

The immunoglobulin class in Waldenstrom’s = IgM

Question 5

Key investigation in MM

Answer 5

Serum protein electrophoresis

Question 6

Annual risk of progression of MGUS to MM?

Answer 6

1%

Question 7

Diagnostic criteria for MGUS

Answer 7

Serum paraprotein <30g/L
Plasma cells in BM <10%
no crab
Free light chain ratio <100

Question 8

Smouldering myeloma diagnostic criteria

Answer 8

Serum paraprotein >30g/L
Plasma cells in BM 10-60%
NO CRAB
Free light chain ratio <100

Question 9

Progression rate to MM of smouldering myeloma

Answer 9

10%

Question 10

CRAB criteria

Answer 10

Calcium >2.75mmol/L
Renal disease: creatinine >177umol/L or eGFR <40l/min
Anamiea Hb <100g/L
Bone disease: lytic lesions on imaging

Question 11

What can be seen on blood film of pt with MM?

Answer 11

Rouleaux formation

Question 12

What is the most common cause of renal injury in MM?

Answer 12

Free light chains

Question 13

Myeloma diagnostic workup

Answer 13

1. Immunoglobulin studies (Serum protein electrophoresis, serum FLC levels, 24hr urinary BJP)
2. BM aspirate and biopsy (IHC)

Question 14

In immunohistochemistry in MM, what markers are useful?

Answer 14

CD138 = Plasma cell marker
CD56 = MYELOMA SPECIFIC

Question 15

Myeloma staging system

Answer 15

Revised- International staging system

Question 16

Immunophenotyping results in MM

Answer 16

CD138+, CD38+, CD56+, Cytoplasmic Ig, Kappa or lamda light chain restriction

NEGATIVE: CD19, CD20, Surface Ig

Question 17

Types of treatments for MM

Answer 17

Alkylating agents, proteasome inhibitors, immunomodulatory drugs, steroids, MoAbs

Question 18

Bortezomib - drug class?

Answer 18

Proteasome inhibitor (particuarly good in MM renal disease)

Question 19

First line MM drug in relapse?

Answer 19

Bortezomib

Question 20

Example of alkylating agent

Answer 20

Melphalan

Question 21

Example of IMIDs

Answer 21

Thalidomide, lenalidomide

Question 22

How does autologous HSCT work in MM?

Answer 22

Stem cells from pt collected, high does melphalan used to kill myeloma cells, reinfusion of stem cells

Question 23

How do proteasome inhibitors work to treat MM?

Answer 23

o All proteins made by the cell will be folded in the ER. If this process goes wrong, misfolded proteins will accumulate in the ER  misfolded proteins are insoluble and don’t function  fatal ER stress  cell death

o Proteasome = large enzyme complex that degrades most intracellular proteins (i.e. damaged proteins)
o If you INHIBIT the proteasome, you will get an accumulation of misfolded proteins in the myeloma cells leading to myeloma cell death

Question 24

Example of MoAb used in MM

Answer 24

Daratumumab - atniCD38

Question 25

Which type of amyloidosis is associated with MM?

Answer 25

AL

Question 26

Which subtype of light chain is commonly involved in MM AL?

Answer 26

Lambda light chain involved in 60%

Question 27

Clinical presentation of MM AL?

Answer 27

Deranged LFTs
nephrotic sx
Unexplained HF
Sensory neuropathy
Macroglossia