Multiple myeloma Flashcards

1
Q

MM is the malignant proliferation of….

A

Plasma cells in the bone marrow –> destroys bone and bone marrow

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2
Q

MM is characterised by high serum …

A

IL6 (plasma cell growth factor)

Stimulates plasma cell growth and immunoglobulin production

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3
Q

List clinical features (mostly investigation findings) of MM

A

Bone

  • Bone pain + hypercalcaemia
  • Lytic lesions especially on vertebrae and skull (don’t come up on bone scan)
  • Pathological fractures

Elevated serum protein - neoplastic plasma cells produce immunoglobulin; M spike (in the gamma region) is present on SPEP, most commonly due to IgA or IgG

Infection - monoclonal ab lacks antigenic diversity; most common cause of death

Rouleaux formation of RBCs on blood film
Normo/macrocytic anaemia

High total protein but low albumin!

Primary amyloid light chain amyloidosis - free light chains are overproduced relative to heavy chains and deposit in tissues

Kidneys
Proteinuria - free light chains are excreted in the urine as bence jones proteins
Renal failure - deposition of free light chains in the kidney tubules lead to kidney failure

Hyperviscosity

  • Confusion, headache, visual changes, mucosal haemorrhage, high output CCF
  • Fundoscopy: flame haemorrhages
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4
Q

What’s monoclonal gammopathy of undetermined significance (MGUS)?

A

Pre-myeloma state

Increased serum protein with M spike on SPEP but no other features e.g. CRAB features of MM

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5
Q

What are the CRAB features of MM?

A

Hypercalcaemia
Renal failure (CrCl <40)
Anaemia (Hb <100)
Bone disease (1+ lytic lesions)

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6
Q

What % of MGUS becomes MM?

A

1% of MGUS develops into MM per year

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7
Q

Do we treat MGUS or smouldering myeloma?

A

No

Treatment is only offered to MM

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8
Q

What’s the difference between smouldering myeloma and MGUS?

A

Both don’t have CRAB features

MGUS has <10% clonal plasma cells in BM
Smouldering has 10-60% clonal plasma cells in BM

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9
Q

How does multiple myeloma differ to smouldering or MGUS?

A

Clonal BM plasma cells ≥10% or ≥1 biopsy-proven plasmacytoma AND 1 or more MM defining events:

  • ≥ 1 crab feature
  • ≥ 1 Biomarker of malignancy
  • —> clonal plasma cell in BM ≥60%
  • —> Serum FLC ratio ≥100 (either kappa or lambda)
  • —> >1 MRI focal lesion ≥5mm on MRI
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10
Q

What will you see on fundoscopy in MM?

A

Flame haemorrhages due to hyperviscosity

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11
Q

Rx for hyperviscosity in MM

A

Plasmapharesis

If IgM >50g/L, IgA >70g/L, IgG >100g/L is a medical emergency

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12
Q

Which is the most viscous? IgM, IgA, IgG?

A

IgM > IgA > IgG
Hence Waldenstrom macroglobinemia is the most likely to produce hyperviscosity since it predominantly produces IgM antibodies

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13
Q

Standard investigations for MM

A

FBC, blood film
Biochem including creatinine and calcium
SPEP + immunofixation (more sensitive than SPEP at picking up small M proteins)
UPEP + immunofixation - Bence Jones proteins
BM biopsy and aspirate
Cytogenetics (metaphase karyotype & FISH)
Serum b2 microglobulin prognosis
LDH prognosos
Serum free light chains
- Measures free lambda & kappa light chains
- Measures kappa/lambda ratio
- sFLC may go up in renal failure or immune activation. If the ratio is abnormal, then its monoclonal polyclonal disorders

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14
Q
What would you expect to see in MM?
1) FBC
2) Film
C) Biochem
4) LDH
A

1) normocytic/macrocytic anaemia, cytopenias
2) rouleaux, circulating plasma cells
3) Raised creatinine and calcium, raised total protein, low albumin
4) High LDH in aggressive disease

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15
Q

How does MM cause renal impairment?

A

1) myeloma cast nephropathy - light chains and paraprotein are filtered through glomerulus –> go through tubules where they complex with tamm-horsfall protein –> form casts –> block tubules

2) Light chain deposition disease
Light chains and paraproteins also trigger inflammatory cascade –> damaging to proximal tubule cells

3) Amyloidosis
4) Acquired fanconi
5) Hypercalcaemia
6) Hyperuricaemia

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16
Q

Fit, age <70yo = transplant candidate

How to treat MM?

A

Induction: bortezomib (protease inhibitor), lenalidomide and dexamethasone (triple therapy)
+ ASTC

Maintenance: lenalidomide

17
Q

Unfit, age >70yo = non-transplant candidate

How to treat MM?

A

Same as fit people but no ASTC

Induction: bortezomib, lenalimode and dexamethasone

18
Q

Who gets treatment in myeloma?

A

Myeloma and very high risk smouldering myeloma

19
Q

Supportive therapies in myeloma

A

Bisphosphonate

Transfusion (anaemia)

S/C IVIG replacement

Valciclovir prophylaxis - VZV infection risk is high on bortezomib

20
Q

Relapse myeloma Rx

A

Carfilzomib (proteosome inhibitor) + dexamethasone +/- lenalidomide

Daratumumab (CD30 ab) + bortezomib (proteosome inhibitor) + dexamethasone