Multiple myeloma

Question 1

What is multiple myeloma?

Answer 1

• Type of bone marrow cancer
• It is a malignant plasma cell (post-germinal B cell) dyscrasia characterized by the proliferation of abnormal plasma cells in the bone marrow.
• These plasma cells secrete monoclonal antibodies (most commonly of the Ig subtype) and antibody fragments into the serum and the urine.
• It’s called multiple myeloma as the cancer often affects several areas of the body, such as the spine, skull, pelvis and ribs.

Question 2

How is multiple myeloma classified?

Answer 2

Classified based on immunoglobulin type → IgG and IgA for the majority of patients

Question 3

What are the risk factors for multiple myeloma?

Answer 3

• Age > 60.  
• Male
• Genetic predisposition
• Immunosuppressive conditions
• Black people 2x white people
• Exposure to radiation or chemicals (asbestos, benzene, pesticides) 
• Monoclonal gammopathy of undetermined significance (MGUS)[a non-cancerous condition where the body makes an abnormal protein, called a paraprotein] a person with a small amount of M protein in their blood has a 1% to 2% chance of developing myeloma

Question 4

What are the presenting symptoms of multiple myeloma?

Answer 4

1. Bone Pain → especially back pain. Can lead to pathological fractures.
2. Anaemia → as bone marrow becomes suppressed. Can lead to fatigue and SOB.
3. Hypercalcaemia (reduces neuromuscular excitability) → abdominal pain, constipation, nausea, anorexia, confusion, polyuria, polydipsia.
4. Renal Impairment → ATN = dehydration and increasing thirst. (Acute tubular necrosis (ATN) is a kidney disorder involving damage to the tubule cells of the kidneys)
5. Infection

Question 5

What signs of multiple myeloma can be found on physical examination?

Answer 5

Pallor, tachycardia, flow murmur, signs of heart failure, dehydration. Purpura, hepatosplenomegaly, macroglossia, carpal tunnel syndrome and peripheral neuropathies.  

CRAB HAI:
C= HyperCalcaemia: increased osteoclast-mediated bone reabsorption.
R= Renal impairment: e.g. light chain deposition in the kidneys and hypercalcaemia.
A= Anaemia
B= Bone pathology: osteolytic lesions - pathological fractures and vertebral compression fractures.
H= Hyperviscosity (blood thickening- can be due to increased RBC): headache, visual disturbances, and thrombosis.
A= Amyloidosis: cardiac failure and neuropathies.
I= Infection: recurrent infection occurs secondary to leukopenia and immunoparesis (there is low levels of functional IgG).

Question 6

What investigations are used to diagnose/ monitor multiple

Answer 6

1. Serum or Urine Electrophoresis → best initial test. Raised concentrations of monoclonal IgA/IgG proteins will be present in the serum. (Will have one type of Ig being produced in excess - monoclonal band seen). Bence Jones proteins may be seen in urine.
2. Bone Marrow Aspirate and Biopsy → confirmatory test. Increased plasma cells in the bone marrow ≥10%.
3. Bloods → anaemia, thrombocytopenia, raised urea & creatinine (due to renal impairment), raised calcium (low PTH due to -ve feedback)
4. Rouleaux Formation → stacking of red blood cells seen on blood film
5. Whole Body MRI or CT → look for bone lesions

Question 7

How is multiple myeloma managed?

Answer 7

1. Stem Cell Transplant eligible → induction therapy (thalidomide + dexamethasone) followed by autologous stem cell transplantation
2. Stem Cell Transplant ineligible → chemotherapy alone

Question 8

What complications may arise from multiple myeloma?

Answer 8

1. Bone Disease: Multiple myeloma often leads to bone destruction, pathological fractures, and skeletal-related events. Treatment includes bisphosphonates and denosumab to strengthen bones.
2. Renal Dysfunction: Kidney impairment is a common complication, requiring close monitoring and potential interventions.
3. Infections: Patients with myeloma are at increased risk of infections due to weakened immune function. Preventative measures and prompt treatment are essential. Influenza and pneumococcal vaccination should be given for infection prevention.
4. Anaemia: Should be managed with erythropoietin (± transfusion) for anaemia

Question 9

Describe the prognosis of multiple myeloma

Answer 9

Incurable disease. Patients relapse 2 to 5 years after treatment. 

Question 10

Describe the epidemiology of multiple myeloma

Answer 10

• M>F, median age of presentation is at 70 yrs old
• Multiple myeloma is the second most common haematologic malignancy, accounting for approximately 1% of all cancers.
• those of Afro-Caribbean descent are affected twice as frequently as Caucasians