Multiple Myeloma Flashcards
What is the mnemonic for multiple myeloma?
CRAB
Calcium elevation
Renal insufficiency/kidney impairment
Anaemia
Bone disease
What are the subtypes of multiple myeloma?
50% IgG
20% IgA
20% kappa or lambda light chain
What causes anaemia in multiple myeloma?
Dilution by M/paraprotein
BM replacement
Relative EPO deficiency (in part due to kidney damage)
What is multiple myeloma?
A haematological cancer characterised by clonal proliferation of plasma cells in the bone marrow and presence of a monoclonal immunoglobulin (or fragment) in the serum and urine
What are the most common presenting features of MM?
Bone pain and anaemia
Are males or females more likely to get MM?
Men
What is the typical age of diagnosis of MM?
69
What is the pathophysiology of MM?
Arises from post-germinal B cells in the lymph node with extensive somatic hypermutation and class switching of heavy chain genes suggesting that the plasma cells have undergone antigen selection
MM cells usually secrete Ig or Ig fragments in urine or plasma
However, normal Ig is impaired so you have a relative hypogammaglobulinaemia and are predisposed to infections
What is the common translocation mutation involved in MM?
14q32
What mutation is associated with a poor prognosis in MM?
Chr 17p deletion
Chr 13 deletions
What is the pathogenesis of bone disease?
Adhesion molecules mediate the homing of myeloma cells to the bone marrow and adhesion to BM stromal cells and ECM.
Cytokines stimulate osteoclastgenesis and osteoclast activity + impair osteoblast formation –> osteolytic bone disease and hypercalcaemia
What are the symptoms of hypercalcaemia?
Bones, stones, groans, psychiatric moans
Bone pain
Kidney stones
Abdominal groans (constipation, nausea, indigestion)
Psychiatric moans: depression, memory loss
When is MM suspected?
- Bone pain with lytic lesions
- Increased total serum protein concentration and/or the presence of monoclonal (M) protein in the serum or urine
- Systemic signs suggestive of malignancy e.g. unexplained anaemia
- Hypercalcaemia
- Acute kidney failure
What are the diagnostic criteria of MM?
- Clonal BM plasma cells >10%
PLUS one of the following
- Presence of related organ or tissue impairment (CRAB)
- Presence of a biomarker associated with near inevitable progression to end organ damage (SLiM = sixty, light chain ratio, MRI)
>60% clonal plasma cells in BM
FLC ratio of 100 or more
MRI with more than one focal lesion
What are the symptoms of MM?
Anaemia
Bone pain
Infections
Fatigue (anaemia or hyperCa)
Renal impairment
What Ix do you do for MM?
Routine UA
FBC- anaemia
Serum calcium, creatinine, albumin, LDH, beta2 microglobulin (B2M) (helpful for prognosis)
Serum/urine protein electrophoresis: serum M protein elevated (IgG or IgA)
Serum/urine immunofixation: to determine the paraprotein immunoglobulin type: IgG, IgA or kappa or lamba light chain are most common)
Serum free light chain assay (FLC assay) increased
BM aspirate and biopsy: immunophenotyping, cytogenetics
Whole body low dose CT or MRI
What are some of the major toxic complications for MM?
Infective episodes (rarely sepsis)
DVT (use aspirin or a NOAC)
Neuropathy
What are the general management considerations of MM?
Ensure treatment of bone disease (bisphosphonates or denosumab)
Analgesia
Hydration to prevent renal failure
DVT prophylaxis
1st line= stem cell transplant
2nd line= use of the induction drugs + maintenance regime
- Dexamethasone, thalidomide, bortezombib etc
3rd line = combination and novel agents
- Carfilzomib
- isatuximab
What is the management for stem cell transplant of MM?
Stem Cell Transplant!
1st line; induction therapy
- Non-chemo more popular: dexamethasone, thalidomide, bortezomib etc
Conditioning; melphalan
Stem cell transplant
