Affects primarily middle-aged and elderly patients.
Recognize complications that require prompt intervention.
A symptomless patient is usually not treated, whereas a symptomatic patient is actively treated.
Pathology
MM is a malignant clonal proliferation of mature B cells (plasma cells). Clonal plasma cells only produce one monotonous type of immunoglobulin (M component, a paraprotein).
The paraprotein may either be a complete immunoglobulin (including both heavy and light chains) or it may be composed of light chains only.
The most common paraprotein is IgG kappa/lambda, followed by IgA kappa/lambda and pure light chain paraprotein in order of frequency. IgD kappa/lambda is rare, and IgM paraprotein is almost without exception associated with Waldenström's macroglobulinaemia. IgM myeloma is extremely rare.
In rare cases, more than one paraprotein can be identified, and in some cases (< 3%) the tests remain negative for paraproteins.
Epidemiology
Approximately 5 new cases/100 000/year.
The disease affects middle-aged and elderly persons; the age at the time of diagnosis is 68-70 years on average. 10% of the patients are less than 50 years old, and 2% are less than 40 years old.
Unknown. However, many changes typical of myeloma can be identified in the chromosomes of the bone marrow; these also affect the prognosis of the disease.
Diagnostic criteria of myeloma
Both of the following two criteria have to be met for a myeloma that requires treatment.
At least 10% clonal plasma cells on bone marrow biopsy or biopsy-confirmed extramedullary plasmacytoma
End-organ damage ("CRAB") attributable to myeloma
Hypercalcaemia (C)
Renal insufficiency (R)
Anaemia (A)
Lytic bone lesions (B)
Clonality is demonstrated either by flow cytometry or immunohistochemically.
Myeloma diagnosis can also be established without CRAB symptom if bone marrow clonal plasma cells are ≥ 60%, or if bone marrow plasma cells are ≥ 10% and the serum free light chain ratio is clearly abnormal (≥ 100, and the concentration of the abnormal free light chain should be at least 100 mg/l) or skeletal MRI studies show a > 5 mm focal change.
Differential diagnostics
Smoldering myeloma (does not require treatment)
Serum paraprotein ≥ 30 g/l and 10-60% plasma cells in the bone marrow, but no end-organ damage and no amyloidosis
Usually follow-up without treatment
Monoclonal gammopathy of undetermined significance (MGUS)
Paraprotein < 30 g/l, no end-organ damage
Plasma cells in bone marrow < 10%
Follow-up without treatment
Solitary plasmacytoma
< 10% clonal plasma cells in the bone marrow, no other bone changes, no end-organ damage
The paraprotein is IgM and the bone marrow is infiltrated by lymphocytic cells, no bone changes.
Lymphomas associated with a paraprotein
Clinical picture
Often
Osteolytic lesions and bone pains
Anaemia, hypercalcaemia, hyperuricaemia
Renal insufficiency
Plasmacytoma located in soft tissue
Rarely
Hyperviscosity syndrome (especially IgA myeloma)
Typical laboratory findings
Increased erythrocyte sedimentation rate (not in light-chain myeloma)
Paraprotein in serum and/or urine, either of the serum free light chains (kappa/lambda) elevated and their ratio abnormal
Decreased haemoglobin level, often also leuco- and thrombocytopenia
Malignant plasma cell infiltrates in the bone marrow
Osteolytic lesion in bone x-ray
Often increased plasma urate and calcium but diminished albumin concentration
Basic examinations
Basic blood count with platelets, plasma calcium, potassium, sodium and creatinine and ESR
Bone marrow examination
Serum protein electrophoresis and serum free light chains
Additional investigations when MM is certain or likely
Radiological assessment: low-dose CT, if available (without contrast medium), or plain X-rays (skull, thorax/ribs, vertebrae, scapulae, pelvis and long bones of the extremities)
Plasma total protein, albumin, urate and immunoglobulins (IgG, IgA, IgM, sometimes IgD), serum free light chain assay, urinary light chains
Paraprotein typing by immunofixation
Magnetic resonance imaging is more sensitive than radiography, but is seldom indicated in basic diagnosis. Scintigraphy usually does not reveal lytic changes.
Complications requiring immediate attention
Sepsis or pneumonia (intravenous broad-spectrum antimicrobial drug)
Myeloma can be classified as a low-risk, an intermediate-risk or a high-risk disease based on e.g. chromosomal changes, amount of paraprotein, haemoglobin concentration, renal damage, and concentrations of calcium, albumin and beta-2-microglobulin.
Risk classification has a great impact on prognosis; the median life expectancy varies from 2 years to over 10 years. The average life expectancy of a patient diagnosed with myeloma has in any case been almost doubled during the past 20 years, being now about 7-8 years.
Myeloma cells become gradually resistant to chemotherapy.
Cytopenias, Infections and renal insufficiency frequently make the disease worse.
Follow-up and treatment
If the patient is symptomless, no specific therapy is usually given.
Symptomatic patients are treated actively.
In follow-up, attention is paid to
the amount of paraprotein
the blood picture (reflects the degree of bone marrow infiltrates)
general condition and symptoms, infections and (bone) pains
osteolytic lesions (x-ray)
renal function and hypercalcaemia.
Follow-up of patients with MGUS (symptoms, general condition and determination of paraprotein or the immunoglobulin involved) is carried out in primary health care.
Pharmacological treatment of myeloma
Many myeloma drugs with new mechanisms of action have become available alongside of the traditional cytotoxic agents. This also makes the treatment choices more difficult, and therefore it is advisable that these are made by haematologists or specialists in internal medicine who are familiar with the treatment of haematological diseases.
Intensive therapy with the support of autologous stem cell transplantations is the first-line treatment for patients under 70(-75) years. In young patients (< 50-60 years) with a genetic profile predicting poor prognosis, also allogeneic stem cell transplantation can sometimes be considered.
Myeloma treatment almost always includes a glucocorticoid(usually dexamethasone) together with different combinations of the following myeloma drugs:
Pneumococcal and influenza vaccinations in patients with myeloma should be taken care of.
If the treatment includes a high-dose glucocorticoid, Pneumocystis jirovecii prophylaxis must be taken care of (sulpha-trimethoprim, dapsone, pentacarinat).