Overview
Multiple myeloma is a plasma cell neoplasm: a condition involving clonal expansion of plasma cells that secrete paraprotein or free light chains.
Unlike monoclonal gammopathy (MGUS) or smouldering myeloma, multiple myeloma involves end-organ dysfunction.
Manifestations
Multiple myeloma presents classically with hypercalcaemia, renal dysfunction, anaemia and lytic bony lesions (denoted by the acronym CRAB); myeloma should be suspected in patients with any of these manifestations without any other clear cause.
Manifestations of Multiple Myeloma
Classical (CRAB)
- Calcium - hypercalcaemia
- Renal failure (multifactorial) - due to cast nephropathy, glomerular light chain deposition, hypercalcaemia, amyloidosis
- Anaemia - normocytic, normochromic
- Bone lesions - lytic lesions, due to osteoclastic change
Other
- Hyperviscosity syndrome - due to hypergammaglobulinaemia
- Amyloidosis - GI, cardiac, hepatic, renal, muscular or nerve infiltration
- Recurrent infections - due to relative hypogammaglobulinaemia
Diagnosis
History
- Constitutional symptoms - fatgue, lethargy, fevers
- Symptoms of anaemia - fatigue, lethargy, lightheadedness, exertional dyspnoea, worsening angina, headache
- Symptoms of hypercalcaemia - lethargy, confusion, nausea, reflux, constipation, renal stones
- Bone pain
- Hyperviscosity syndrome - neuropathy, epistaxis, blurred vision, headache
- Recurrent infections
Examination
- Signs of anaemia - conjunctival pallor, pale hand creases, tachycardia
- Mucosal bleeding
- Sepsis
Investigations
Myeloma Screen
- Serum immunoglobulins - may demostrate elevation of a single Ig
- Serum free light chains - abnormally high or low kappa : lambda ratio
- Serum protein electrophoresis - demonstrating a monoclonal band
- Serum immunofixation electrophoresis - presence of paraprotein
Other Tests for Suspected Myeloma
- FBC - cytopaenias
- Blood film - normocytic normochromic anaemia with rouleaux
- EUC - renal failure
- Uric acid
- CMP - hypercalcaemia
- Albumin - hypoalbuminaemia
- LFT - elevated ALP
- Beta-2 microglobulin - for staging
- Skeletal survey (x-ray or CT) - for lytic lesions
- Bone marrow biopsy - for morphology, cytogenetics and FISH
Management
Multiple myeloma must be referred to a haematologist for management.
The treatment of multiple myeloma involves induction therapy, followed by autologous stem cell transplants in eligible patients. Choice of chemotherapy depends on multiple clinical factors including functional (ECOG) score, severity and whether the patient is recieving a stem cell transplant.
It is also important to treat the manifestations of myeloma such as hypercalcaemia, bony lesions and recurrent infections.
Stages of Multiple Myeloma Treatment
- Initiation - generally with combination chemotherapy
- Autologous stem cell transplant - in eligible patients
- Maintenance therapy - with a single agent or combination chemotherapy
- Relapsed multiple myeloma - complex; multiple treatment options including clinical trials
Common Regimens Used in Multiple Myeloma
Single Agent Therapies
- Imide immunomodulators - thalidomide / lenalidomide
- Proteasome inhibitors - carfilzomib / bortezomib
Combination Therapies
- Lenalidomide/dexamethasone (RD)
- Bortezomib/lenalidomide/dexamethasone (VRD)
- Bortezomib/thalidomide/dexamethasone (VTD)
- Bortezomib/cyclophosphamide/dexamethasone (VCD/CyBorD)
- Carfilzomib/lenalidomide/dexamethasone (KRD)
- Melphalan/prednisone/lenalidomide (MPL)
Other Measures
- Manage hypercalcaemia - fluids, steroids, bisphosphonates
- Manage skeletal lesions - bisphosphonates, radiotherapy, surgery
- Manage hyperviscosity - fluids, leukopheresis
Next Page
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------