Multiple Myeloma

Question 1

what does MGUS stand for? what does it mean?

Answer 1

monoclonal gammopathy of undetermined signficance

it’s where there is an elevation of of a single type of immunoglobulin in the body but does not produce any physical s/s

premalignant state

Question 2

how does MGUS present?

Answer 2

asymptomatic

most of the time MGUS is dx incidentally when an serum protein electrophoresis (SPEP) is ordered for another indication

Question 3

types of MGUS?

Answer 3

there is IgM MGUS (2nd most common), there is non-IgM MGUS (IgG is most common), and there is light chain MGUS

Question 4

how is MGUS dx? how is it characterized? (4)

Answer 4

using a serum protein electrophoresis

1. Serum monoclonal protein < 30 g/L (3 g/dL)
2. < 10% of clonal plasma cells in the BM
3. Absence of CRAB symptoms (hypercalcemia, renal insufficiency, anemia and, bone lesions suspicious for MM)

Question 5

how to manage MGUS

Answer 5

conservatively, just arrange for regular follow-ups with serum M protein labwork

and pt education on signs to look out for what multiple myeloma may look like

Question 6

what is smouldering myeloma?

Answer 6

precancerous condition

serum M protein >= 3 g/dL but still asymtomatic

Question 7

what is multiple myeloma?

Answer 7

abnormal/malignant proliferation of ineffective monoclonal immunoglobulins via one plasma cell in the bone marrow

whereby >10% of the BM contains plasma cells

Question 8

patho of multiple myeloma

Answer 8

1. MGUS
2. unknown transformation by gaining a “second” hit from MGUS ➔ smoldering myeloma ➔ multiple myeloma
3. activation of an oncogene or inactivation of a tumour suppressor gene
4. increase in plasma cell proliferation resulting in the monoclonal expansion of a single plasma cell/immunoglobulin
5. large spike of M protein

Question 9

what are some s/s of multiple myeloma?

Answer 9

constitutional s/s
the big warning sign is persistent back, flank, or rib pain that is worse at night + BM changes/dysfunction

Constitutional symptoms (CRAB):
- hyperCalcemia: moans, groans, throne, bones, psychiatric overtones
- Renal dysfunction: edema, acidosis, electrolyte disturances
- Anemia: fatigue, weakness, pallor
- Bone pain w/lytic lesions: bone pain, pathological fractures, spinal cord compression, kyphosis

other
- hyperviscosity syndrome (MEDICAL EMERGENCY): from increase amount of immunoglobulins in circulation ➔ bleeding, hypoperfusion, neurologic s/s, confusion, HF, vision changes
- recurrent infections ➔ depleted functional immunoglobulin stores

Question 10

what is M protein?

Answer 10

stands for monoclonal protein

they can be produced by abnormal, cancerous, or precancerous cells

Question 11

what diseases can cause an M protein spike on a serum protein electrophoresis?

Answer 11

chronic leukemia
B/T cell lymphomas
any plasma cell dyscrasias

Question 12

RF for multiple myeloma

Answer 12

• MGUS
• obesity
• exposure: alcohol, benzene, pesticides, radiation
• FHx of multiple myeloma/genetics
• African American
• male
• increased age

Question 13

diagnostic test for multiple myeloma

Answer 13

1. bone marrow biopsy: >= 10% clonal plasma cells
2. at least one of the slim crab criteria (besides the BM)
   - Sixty percent plasma cells in BM specimen
   - Light chain ratio >100
   - MRI lytic lesion >0.5 cm
   - Calcium >2.80 mmol/L
   - Renal failure (Cr >176 mmol/L)
   - Anemia
   - Bony lesions (lytic lesions or osteoporosis felt to be caused by myeloma)

Question 14

other investigations to order when working up a multiple myeloma dx

Answer 14

Bloodwork
- CBC
- PBS ➔ Rouleaux formation (stacked coin appearance)
- electrolytes + extended lytes
- renal function and liver function
- LDH
- serum protein electrophoresis + immunofixation (tells you type of Ig)
- free light chain assay

Urine
- urine protein electrophoresis (Bence-Jones proteinuria) or 24h protein
- light chain assay in urine

Imaging
- whole body CT/MRI or XR ➔ look for bony lytic lesions

Other
- BM biopsy ➔ immunohistochemistry and flow cytometry and cytogenetics

Question 15

how to tx multiple myeloma

Answer 15

induction therapy: chemo combo can include alkylating agents, antitumour abx, immunomodulators, and steroids

autologous stem cell transplant

maintenance therapy w/ proteasome inhibitor or immunomodulators

manage s/s
- C - fluids, calcitonin or bisphosphonates
- R - adjust renal toxic drugs + fluids
- A - transfusions or EPO
- B - radiation, bisphosphonates

Consider LMWH for hyperviscosity and prophylaxtic abx for infection risk