Multiple myeloma (CH)

Question 1

What is multiple myeloma?

Answer 1

Haematological incurable malignancy characterised by plasma cell proliferation (results in excessive monoclonal immunoglobulin production) and infiltration of bone marrow by plasma cells

Question 2

Describe the epidemiology of multiple myeloma. (2)

Answer 2

• median age: 70
• M>F

Question 3

How is multiple myeloma classified?

Answer 3

• based on immunoglobulin type
• majority of patients are IgG and IgA

Question 4

What are some contributing mechanisms to multiple myeloma?

Answer 4

Immunoglobulin (Ig) gene rearrangement, extensive somatic hypermutation + class switching of immunoglobulin heavy chain (IgH) genes

Question 5

Describe the pathophysiology of multiple myeloma?

Answer 5

Myeloma cells proliferate and accumulate in the bone marrow, and secrete abnormal monoclonal immunoglobulins or immunoglobulin fragments (paraprotein or M-protein) –> hypercalcaemia, osteolytic bone disease, renal failure, anaemia and infection

Question 6

What are the most common presenting features of multiple myeloma?

Answer 6

Bone pain and anaemia

Condition may also be identified through Ix of fatigue, infections, hypercalcaemia or renal impairment

Question 7

What are the clinical features of multiple myeloma?

Answer 7

CRABBBI

• hyperCalcaemia (reduces neuromuscular excitability) - stones, abdominal groans, psychic moans
• Renal impairment - light chain deposition within renal tubules causes renal damage (acute tubular necrosis) –> dehydration and thirst
• Anaemia (bone marrow suppression) - fatigue, SOB
• Bone pain/fracture (osteoporosis) - especially back pain
• B symptoms (fever, WL, night sweats)
• Bleeding & Bruising - thrombocytopenia
• Infection - Increased susceptibility

Question 8

What symptoms of hypercalcaemia are seen in multiple myeloma? (7)

Answer 8

Stones, thrones, abdominal groans, psychic moans

• abdominal pain
• constipation
• nausea
• anorexia
• confusion
• polyuria
• polydipsia

Question 9

How does renal impairment occur in multiple myeloma, and how does this present?

Answer 9

Light chain deposition within renal tubules causes renal damage (acute tubular necrosis)

• dehydration
• increasing thirst

Question 10

What drugs can precipitate renal impairment in multiple myeloma?

Answer 10

NSAIDs e.g. naproxen

Question 11

What are some risk factors for multiple myeloma? (5)

Answer 11

• peak incidence - 70s
• Afro-Caribbeans > White > Asian
• monoclonal gammopathy of undetermined significance (MGUS) - plasma cells make abnormal protein (paraprotein/M protein) in bone marrow (harmless condition)
• abnormal free light chain ratio (Kappa/Lambda ratio <0.26 or >1.65) - prognostic
• family history

Question 12

What are the first-line investigations for multiple myeloma? (2)

Answer 12

• urine/serum protein electrophoresis
• bone marrow aspirate + biopsy

Question 13

What is the best initial test for multiple myeloma, and what would we see?

Answer 13

Urine/serum protein electrophoresis

• serum - raised concentrations of monoclonal IgA/IgG proteins - will have one type of Ig being produced in excess (monoclonal band seen)
  
  • paraprotein identified (2/3 IgG, 1/3 IgA)
  • hypogammaglobulinemia
• urine - Bences jones proteins (monoclonal free light chains)

Question 14

What is the confirmatory test for multiple myeloma, and what do we see?

Answer 14

Bone marrow aspirate and biopsy - increased monoclonal plasma cells in bone marrow >10%

• plasma cells - large cells with perinuclear halo, eccentric nuclei, blue cytoplasm
• differentiate multiple myeloma from monoclonal gammopathy of undetermined significance (MGUS) and solitary plasmacytoma

Question 15

What would bloods show in multiple myeloma? (7)

Answer 15

• anaemia - normocytic
• thrombocytopenia + pancytopenia
• raised urea and creatinine (renal impairment)
• raised calcium (low PTH due to -ve feedback), normal/high phosphate, normal ALP
• raised ESR (may have normal CRP)
• serum beta2-microglobulin + serum albumin (prognostic factors)
• serum free light-chain assay (increased concentration)

Question 16

What would a blood film show in multiple myeloma?

Answer 16

Rouleaux formation - stacking of RBCs

Question 17

What scan is needed to be done in multiple myeloma?

Answer 17

Whole body MRI to look for bone lesions / low-dose CT

Question 18

What might you see on XR in multiple myeloma?

Answer 18

Raindrop skull (multiple osteolytic lesions) - pattern rain forms after hitting surface and splashing –> random pattern of dark spots

(NB subtly different finding in primary hyperparathyroidism - ‘pepperpot skull’)

Question 19

What is the diagnostic criteria for multiple myeloma?

Answer 19

1 major + 1 minor OR 3 minor criteria:

• major:
  
  • plasmacytoma (biopsy)
  • 30% plasma cells in BM sample
  • elevated M protein in blood/urine
• minor:
  
  • 10-30% plasma cells in BM sample
  • minor elevations in M protein in blood/urine
  • osteolytic lesions (imaging)
  • low levels of antibodies (not produced by cancer cells) in blood

Question 20

What are some differential diagnoses for multiple myeloma? (7)

Answer 20

• monoclonal gammopathy of undetermined significance (MGUS) - asymptomatic, no end-organ damage
• solitary plasmacytoma - localised bone pain or soft-tissue swelling
• Waldenstrom’s macroglobulinaemia
• amyloidosis
• heavy chain disease - lymphadenopathy and hepatosplenomegaly
• non-Hodgkin’s lymphoma - B Sx
• prostatic malignancy - hypercalcaemia and renal impairment

Question 21

What two staging systems are used for multiple myeloma?

Answer 21

• Durie and Salmon staging system - stages I-III, A (normal renal function) creatinine<2mg/dL or B (abnormal renal function)
• International Staging System (ISS) for multiple myeloma - stages I-III based on beta2-microglobulin (I<3.5, III>5.5)

Question 22

What is the management plan for newly diagnosed stem cell transplant candidates in multiple myeloma? (<65 + good performance status)

Answer 22

• induction therapy (thalidomide + dexamethasone)
• followed by autologous stem cell transplantation

Question 23

What is the management plan for patient ineligible for stem cell transplant in multiple myeloma?

Answer 23

Chemotherapy alone (induction therapy) - thalidomide, dexamethasone and melphalan (cyclophosphamide)

Question 24

How do we manage previously diagnosed multiple myeloma that is responding to treatment?

Answer 24

Maintenance with thalidomide

Question 25

How do we manage refractory multiple myeloma?

Answer 25

Combination therapies (lenalidomide and dexamethasone)

Question 26

What drug classes do we stop in multiple myeloma?

Answer 26

Stop thiazide diuretics

NSAIDs can cause renal failure in MM

Question 27

What can we give for DVT prophylaxis in multiple myeloma?

Answer 27

Aspirin

Question 28

What do we give if bone disease in multiple myeloma?

Answer 28

Bisphosphonates (zoledronic acid)

Or denosumab (monoclonal AB that targets RANKL receptor) - preferred in renal impairment

Question 29

What is important in multiple myeloma to prevent renal failure?

Answer 29

Hydration

Question 30

What are some complications of multiple myeloma? (9)

Answer 30

• pancytopenia, thrombocytopenia, leukopenia, anaemia
• VTE
• pathological/compression fractures (e.g. of vertebral bodies, SC compression)
• renal failure
• neuropathies
• hypercalcaemia
• hyperviscosity
• cardiac failure
• amyloidosis

Question 31

Describe the prognosis of multiple myeloma.

Answer 31

Incurable disease - patients will inevitably relapse 2-5 years after treatment