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Haematologic Malignancy
 
Haematologic Malignancy
 

Multiple Myeloma

 
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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
 
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