Multiple Myeloma Flashcards
Multiple myeloma refers to a malignant disorder of … cells (mature B lymphocytes).
Multiple myeloma refers to a malignant disorder of plasma cells (mature B lymphocytes).
Multiple myeloma
Multiple myeloma (MM) is the second most common haematological malignancy. It is characterised by excess secretion of a monoclonal antibody. We term it a monoclonal antibody, because it is derived from a single clone of plasma cells that have undergone abnormal proliferation.
MM accounts for 60-70 cases per 1,000,000 people each year, although the overall prevalence of the condition is increasing due to the improved survival with newer treatments. Unfortunately, it still accounts for 2% of cancer-related deaths and it is associated with a number of severe complications including spinal cord compression, renal impairment and hypercalcaemia,
Myeloma should be suspected in any patient with typical features, but particularly those over 60 years old with:
Unexplained bone pain (and pathological fractures)
Fatigue
Symptoms of hypercalcaemia: bone pain, abdo pain, constipation, confusion, polyuria
Weight loss
Symptoms of cord compression: back pain, new leg weakness, bladder/bowel dysfunction
Symptoms of hyperviscosity: headache, blurred vision, shortness of breath, mucosal bleeding
Recurrent infections
Screening for myeloma
‘Screening’ for myeloma involves looking for monoclonal antibodies, which are the secretion product of the malignant clones.
MM is usually the result of IgG, IgA or the accompanying light chain. It rarely occurs with IgM.
NOTE: The presence of an IgM monoclonal antibody suggests another haematological malignancy termed Waldenstrom macroglobulinemia.
MM is usually the result of IgG, IgA or the accompanying light chain. It rarely occurs with IgM.
NOTE: The presence of an IgM monoclonal antibody suggests another haematological malignancy termed Waldenstrom macroglobulinemia.
MM is usually the result of IgG, IgA or the accompanying light chain. It rarely occurs with IgM.
NOTE: The presence of an IgM monoclonal antibody suggests another haematological malignancy termed .. macroglobulinemia.
MM is usually the result of IgG, IgA or the accompanying light chain. It rarely occurs with IgM.
NOTE: The presence of an IgM monoclonal antibody suggests another haematological malignancy termed Waldenstrom macroglobulinemia.
Prognosis
MM
MM is an incurable disease with a variable natural history.
Patients with myeloma will invariably relapse following treatment. Subsequent relapses are associated with reducing response to treatment. The median survival is highly variable between patients depending on response to treatment, age of onset and cytogenetic abnormalities.
Beta-2 microglobulin is often used as a prognostic tool in the International Staging System (ISS) for myeloma. This divides patients into three groups (I, II, III) based on serum beta-2 microglobulin and albumin levels, which predicts the median survival.
Stage I: median survival 62 months
Stage II: median survival 44 months
Stage III: median survival of 29 months
Other factors associated with a worse prognosis include high plasma cell counts, high levels of monoclonal antibody in blood/urine or development of complications (e.g. diffuse multiple bone lesions, marked anaemia, hypercalcaemia and renal impairment).
Beta-2 microglobulin is often used as a prognostic tool in the International Staging System (ISS) for myeloma. This divides patients into three groups (I, II, III) based on serum beta-2 microglobulin and albumin levels, which predicts the median survival.
Stage I: median survival … months
Stage II: median survival … months
Stage III: median survival of … months
Beta-2 microglobulin is often used as a prognostic tool in the International Staging System (ISS) for myeloma. This divides patients into three groups (I, II, III) based on serum beta-2 microglobulin and albumin levels, which predicts the median survival.
Stage I: median survival 62 months
Stage II: median survival 44 months
Stage III: median survival of 29 months
How does multiple myeloma develop?
There appears to be two key steps in the pathophysiology of MM: development of monoclonal gammopathy of undetermined significance (MGUS) and progression from MGUS to MM.
Development of MGUS: almost all cases of MM arise from this premalignant plasma cell disorder. Affects 3% of patients > 50 years old. Initial cytogenetic abnormality occurs (inciting event). Thought to be an abnormal plasma cell response to antigen stimulus. Leads to creation of plasma cell clone that secretes a monoclonal antibody. Most will not develop MM.
Progression from MGUS to MM: rate of progression estimated at 1% per year. Further cytogenetic abnormalities and changes to the bone marrow microenvironment occur, which promotes proliferation. Associated with systemic problems due to plasma cell infiltration of bone marrow and excess light chain secretion.
Progression from MGUS to MM: rate of progression estimated at …% per year.
Progression from MGUS to MM: rate of progression estimated at 1% per year.
Presenting clinical features (5) for multiple myeloma
Bone disease: widespread due to clonal proliferation in bone marrow. Seen as lytic lesions on imaging. Can lead to fractures.
Impaired renal function: >50% have raised creatinine at diagnosis. Kidneys affected in multiple ways. Commonly due to light chain nephropathy (tubules blocked by light chain casts).
Anaemia: seen in >90% at some point during disease course. Normal bone marrow destroyed by proliferation of malignant plasma cells. Renal disease may contribute (EPO deficiency).
Hypercalcaemia: MM-induced bone demineralisation. More common in active disease. At high levels (≥ 2.9 mmol/L) should be treated as a medical emergency. See our notes on hypercalcaemia.
Recurrent or persistent bacterial infection: immune dysfunction and hypogammaglobulinaemia due to suppression of normal plasma cell function.
CRAB =
C - calcium levels high
R - renal impairment
A - anaemia
B - bone diseaseC
Myeloma should be suspected in any patient with typical features, but particularly those over 60 years old with:
Unexplained bone pain (and pathological fractures)
Fatigue
Symptoms of hypercalcaemia: bone pain, abdo pain, constipation, confusion, polyuria
Weight loss
Symptoms of cord compression: back pain, new leg weakness, bladder/bowel dysfunction
Symptoms of hyperviscosity: headache, blurred vision, shortness of breath, mucosal bleeding
Recurrent infections
