Multiple myeloma

Question 1

Multiple myeloma is a neoplastic proliferation of bone marrow plasma cells associated with monoclonal antibodies in serum and/or urine. It is characterized by the mnemonic CRAB (____, _____, _______, ________ hence bone pain & patho #)

Multiple myeloma is a disease arising from the malignant transformation of a _________________________.

The differentiating cells of the malignant clone have the morphology of plasma cells and have clonally rearranged immunoglobulin genes that secrete a monoclonal immunoglobulin (IgG/IgA), a monoclonal light chain or both. Such monoclonal proteins are called ________________

Plasma cells can form collections (plasmacytomas) outside the bone marrow in bone or soft tissues which cause focal damage (e.g fracture, spinal cord compression).

Answer 1

hypercalcemia, renal insufficiency, anaemia, bone lytic lesions

terminally differentiated B cell (plasma cell

paraproteins.

Question 2

What are the clinical features of multiple myeloma?

Answer 2

Osteolytic lesions from activation of osteoclasts

• p/w bone pain over lumbar spine (most commonly)
• p/w pathological fractures
• 2’ Hypercalcemia – bones, stones groans moans, thrones

BM failure: Thrombocytopenia and anaemia

Renal Failure: light chains are filtered through tubules into kidney 🡪 toxic to tubules
- Can lead to chronic renal failure from obstruction of distal renal tubules by proteinaceous casts, leading to tubular atrophy and interstitial fibrosis

Hyperviscosity syndrome:

• more commonly seen in IgA Myeloma due to dimerization
• Neurological changes (dizziness, somnolence, coma), cardiac failure and haemorrhage

Recurrent respi tract infections (due to reduced circulating T cells 🡪 increased risk of bacterial infection)

Amyloidosis: In 10% of patients, the abnormally folded paraprotein is converted into deposits of amyloid. P/w peripheral neuropathy, macroglossia, cardiomegaly, diarrhea and carpal tunnel syndrome

Question 3

What is the diagnostic criteria for multiple myeloma?

Answer 3

Monoclonal immunoglobulin protein (paraprotein) in serum >30g/l and/or urine
- Request: immunoglobulin levels and protein electrophoresis

Bone marrow: clonal plasma cells >10% of nucleated cell count or localised collection of plasma cells (plasmacytoma)
- Request: bone marrow aspirate and trephine

Related organ or tissue impairment (CRAB: hypercalcaemia, renal insufficiency, anaemia, bone lesions)
- Request: skeletal survey to look for bony lytic lesions, full blood count, renal function and calcium

Question 4

What is the diagnostic criteria for MGUS– monoclonal gammopathy of uncertain significance?

Answer 4

Presence of a monoclonal protein in the serum or urine but with no evidence of myeloma or amyloid

Usually serum IgG <30g/l and IgA <10g/l; w/ BM plasma cells <10%

With ABSENCE of end-organ damage eg CRAB

Question 5

What is the diagnostic criteria for ‘Smouldering myeloma’ - asymptomatic plasma cell myeloma?

Answer 5

Monoclonal protein in serum at myeloma levels (>30g/l) and/or 10% or more clonal plasma cells in BM

But NO related organ/tissue impairment or myeloma-related symptoms

Question 6

What is the definition of plasma cell leukaemia?

Answer 6

• Rare, particularly aggressive form
• > 2x109/L plasma cells in peripheral blood
• or >20% of the leukocyte differential count

Question 7

What are the investigations performed in patients with multiple myeloma?

Answer 7

Peripheral blood film

• Rouleaux formation (stack-like) suggests protein in the blood are separating red cells
• Leads to raised ESR

Bone Marrow Aspirate
Plasma cells >10%
- Eccentrically placed nucleus, blue cytoplasm, clumped chromatin
- Evidence of clonality (special stains: IHC) e.g. CD138, CD56 positive, light chain restriction

Serum Protein Electrophoresis: looking for monoclonal band

Question 8

What is the Revised International staging system (ISS)

staging of multiple myeloma?

Answer 8

Stage I

• Sβ2M < 3.5 mg/l
• Serum albumin ≥ 3.5 g/dl
• Standard-risk chromosomal abnormalities (CA) by iFISH
• Normal LDH

Stage II: Not R-ISS stage I or III

Stage III:

• Sβ2M ≥ 5.5 mg/L and either
• High-risk CA by FISH OR High LDH

Question 9

What is the management of multiple myeloma?

Answer 9

Supportive Care

• Anaemia: transfusions
• Bone pain: analgesia
• High calcium: fluids, steroids & bisphosphonates
• Vertebral crush fractures (severe pain): vertebroplasty (injecting bone cement into the vertebra to maintain height)

Preventing Complications (bisphosphonates) e.g. pamidronate, Zoledronic acid, clodronate
- Reduce pathological fractures, bone pain & need for analgesics, need for radiotherapy (given to pts with/without bony complications)

Remission: Conventional Chemotherapy

• Melphalan in the elderly
• Combination chemotherapy in patients who are sufficiently fit

Definitive Tx: Stem Cell Transplant

• Autologous stem cell transplant: treatment of choice for most patients
• Allogeneic stem cell transplant if less than 50 – may give chance of cure