Multiple myeloma (CH) Flashcards
What is multiple myeloma?
Haematological incurable malignancy characterised by plasma cell proliferation (results in excessive monoclonal immunoglobulin production) and infiltration of bone marrow by plasma cells
Describe the epidemiology of multiple myeloma. (2)
- median age: 70
- M>F
How is multiple myeloma classified?
- based on immunoglobulin type
- majority of patients are IgG and IgA
What are some contributing mechanisms to multiple myeloma?
Immunoglobulin (Ig) gene rearrangement, extensive somatic hypermutation + class switching of immunoglobulin heavy chain (IgH) genes
Describe the pathophysiology of multiple myeloma?
Myeloma cells proliferate and accumulate in the bone marrow, and secrete abnormal monoclonal immunoglobulins or immunoglobulin fragments (paraprotein or M-protein) –> hypercalcaemia, osteolytic bone disease, renal failure, anaemia and infection
What are the most common presenting features of multiple myeloma?
Bone pain and anaemia
Condition may also be identified through Ix of fatigue, infections, hypercalcaemia or renal impairment
What are the clinical features of multiple myeloma?
CRABBBI
- hyperCalcaemia (reduces neuromuscular excitability) - stones, abdominal groans, psychic moans
- Renal impairment - light chain deposition within renal tubules causes renal damage (acute tubular necrosis) –> dehydration and thirst
- Anaemia (bone marrow suppression) - fatigue, SOB
- Bone pain/fracture (osteoporosis) - especially back pain
- B symptoms (fever, WL, night sweats)
- Bleeding & Bruising - thrombocytopenia
- Infection - Increased susceptibility
What symptoms of hypercalcaemia are seen in multiple myeloma? (7)
Stones, thrones, abdominal groans, psychic moans
- abdominal pain
- constipation
- nausea
- anorexia
- confusion
- polyuria
- polydipsia
How does renal impairment occur in multiple myeloma, and how does this present?
Light chain deposition within renal tubules causes renal damage (acute tubular necrosis)
- dehydration
- increasing thirst
What drugs can precipitate renal impairment in multiple myeloma?
NSAIDs e.g. naproxen
What are some risk factors for multiple myeloma? (5)
- peak incidence - 70s
- Afro-Caribbeans > White > Asian
- monoclonal gammopathy of undetermined significance (MGUS) - plasma cells make abnormal protein (paraprotein/M protein) in bone marrow (harmless condition)
- abnormal free light chain ratio (Kappa/Lambda ratio <0.26 or >1.65) - prognostic
- family history
What are the first-line investigations for multiple myeloma? (2)
- urine/serum protein electrophoresis
- bone marrow aspirate + biopsy
What is the best initial test for multiple myeloma, and what would we see?
Urine/serum protein electrophoresis
- serum - raised concentrations of monoclonal IgA/IgG proteins - will have one type of Ig being produced in excess (monoclonal band seen)
- paraprotein identified (2/3 IgG, 1/3 IgA)
- hypogammaglobulinemia
- urine - Bences jones proteins (monoclonal free light chains)
What is the confirmatory test for multiple myeloma, and what do we see?
Bone marrow aspirate and biopsy - increased monoclonal plasma cells in bone marrow >10%
- plasma cells - large cells with perinuclear halo, eccentric nuclei, blue cytoplasm
- differentiate multiple myeloma from monoclonal gammopathy of undetermined significance (MGUS) and solitary plasmacytoma
What would bloods show in multiple myeloma? (7)
- anaemia - normocytic
- thrombocytopenia + pancytopenia
- raised urea and creatinine (renal impairment)
- raised calcium (low PTH due to -ve feedback), normal/high phosphate, normal ALP
- raised ESR (may have normal CRP)
- serum beta2-microglobulin + serum albumin (prognostic factors)
- serum free light-chain assay (increased concentration)
What would a blood film show in multiple myeloma?
Rouleaux formation - stacking of RBCs
What scan is needed to be done in multiple myeloma?
Whole body MRI to look for bone lesions / low-dose CT
What might you see on XR in multiple myeloma?
Raindrop skull (multiple osteolytic lesions) - pattern rain forms after hitting surface and splashing –> random pattern of dark spots
(NB subtly different finding in primary hyperparathyroidism - ‘pepperpot skull’)
What is the diagnostic criteria for multiple myeloma?
1 major + 1 minor OR 3 minor criteria:
- major:
- plasmacytoma (biopsy)
- 30% plasma cells in BM sample
- elevated M protein in blood/urine
- minor:
- 10-30% plasma cells in BM sample
- minor elevations in M protein in blood/urine
- osteolytic lesions (imaging)
- low levels of antibodies (not produced by cancer cells) in blood
What are some differential diagnoses for multiple myeloma? (7)
- monoclonal gammopathy of undetermined significance (MGUS) - asymptomatic, no end-organ damage
- solitary plasmacytoma - localised bone pain or soft-tissue swelling
- Waldenstrom’s macroglobulinaemia
- amyloidosis
- heavy chain disease - lymphadenopathy and hepatosplenomegaly
- non-Hodgkin’s lymphoma - B Sx
- prostatic malignancy - hypercalcaemia and renal impairment
What two staging systems are used for multiple myeloma?
- Durie and Salmon staging system - stages I-III, A (normal renal function) creatinine<2mg/dL or B (abnormal renal function)
- International Staging System (ISS) for multiple myeloma - stages I-III based on beta2-microglobulin (I<3.5, III>5.5)
What is the management plan for newly diagnosed stem cell transplant candidates in multiple myeloma? (<65 + good performance status)
- induction therapy (thalidomide + dexamethasone)
- followed by autologous stem cell transplantation
What is the management plan for patient ineligible for stem cell transplant in multiple myeloma?
Chemotherapy alone (induction therapy) - thalidomide, dexamethasone and melphalan (cyclophosphamide)
How do we manage previously diagnosed multiple myeloma that is responding to treatment?
Maintenance with thalidomide
How do we manage refractory multiple myeloma?
Combination therapies (lenalidomide and dexamethasone)
What drug classes do we stop in multiple myeloma?
Stop thiazide diuretics
NSAIDs can cause renal failure in MM
What can we give for DVT prophylaxis in multiple myeloma?
Aspirin
What do we give if bone disease in multiple myeloma?
Bisphosphonates (zoledronic acid)
Or denosumab (monoclonal AB that targets RANKL receptor) - preferred in renal impairment
What is important in multiple myeloma to prevent renal failure?
Hydration
What are some complications of multiple myeloma? (9)
- pancytopenia, thrombocytopenia, leukopenia, anaemia
- VTE
- pathological/compression fractures (e.g. of vertebral bodies, SC compression)
- renal failure
- neuropathies
- hypercalcaemia
- hyperviscosity
- cardiac failure
- amyloidosis
Describe the prognosis of multiple myeloma.
Incurable disease - patients will inevitably relapse 2-5 years after treatment
