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22 HOW TO TREAT: A PARAPROTEIN

22 HOW TO TREAT: A PARAPROTEIN

20 MARCH 2026 ausdoc. com. au
Table 3. Summary of the IMWG diagnostic criteria for MGUS, SMM and MM
MGUS SMM MM
Serum paraprotein less than 30g / L or abnormal free light chain ratio of less than 0.26 or greater than 1.65 and Clonal bone marrow plasma cells less than 10 % and No myeloma-defining events
Serum paraprotein 30g / L or greater, or urinary monoclonal protein 500mg or greater / 24hours and / or 10-60 % clonal bone marrow plasma cells and No myeloma-defining events
Clonal bone marrow plasma cells 10 % or greater or one or more biopsy-proven plasmacytoma and One or more myeloma-defining events
Electrophoresis followed by immunofixation
Anti-IgG Anti-IgA Anti-IgM Anti-kappa Anti-lambda
Source: Rajkumar SV et al 2014 7
Box 2. Myeloma-defining events
• The traditional myeloma-defining events can be remembered with the acronym CRAB, and these reflect end-organ damage as a consequence of MM:— C – Increased Calcium.— R – Renal insufficiency.— A – Anaemia.— B – Bony lesion.
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• The definition of myeloma-defining events was expanded in 2014 to include three biomarkers of malignancy that predict an 80 % chance of progression to end-organ damage within two years, so the acronym became SLiM-CRAB. 7— S – 60 % or greater( Sixty) clonal bone marrow plasma cells.— Li – Light chain ratio – involved: uninvolved 100 or greater.— M – MRI detection of one or more skeletal lesions( must be greater than 5mm).
( II)( III)( IV)( V)( VI)
Figure 5. Antibodies with fluorescent markers are added to the electrophoresed serum and are compared to the SPE in figure 4. The bands are matched at the corresponding positions to identify the heavy and light chain responsible for the M-protein. This image demonstrates an IgG Kappa paraprotein.
Table 4. Revised International Staging System( R-ISS)
Stage
Criteria
Median overall
survival
R-ISS I
Serum albumin greater than 35g / L and ß2M less than 3.5mg / L and Normal LDH and No high-risk genetic lesions detected by fluorescence in situ hybridisation( FISH) defined as del17p and / or t( 4; 14) and / or t( 14; 16)
Not reported 81 %
Five-year overall survival
Chaustanley / CC BY 4.0 / bit. ly / 46piJfu
R-ISS II
R-ISS III
Failing to complete criteria for R-ISS I or R-ISS III
ß2M greater than 5.5mg / L and High-risk FISH or High LDH
83 months 62 %
43 months 39 %
Source: Palumbo A et al 2015 8
and if not already performed, is per-
1q21 amplifications are associated
formed on all patients with new diag-
with high-risk disease. Myeloma is
noses. In selected cases, an MRI or PET
not a curable disease, and prognosti-
scan may also be indicated to assess the
cating can be difficult because there
patient’ s skeleton and soft tissues for
is great disease heterogeneity. Treat-
myeloma damage or deposits.
ment response is difficult to predict;
A 24-hour urine collection is per-
however, the mostly widely accepted
formed on patients with a new diag-
model is the Revised International
nosis to assess for the presence of a
Staging System( R-ISS, see table 4).
Bence-Jones protein.
While not relevant to the initial diagnosis of MM, patients with certain chromosomal abnormalities are more likely to relapse or be resistant to therapy. Conventional cytogenetics is
Management
Treatment for myeloma varies and is individualised based on the patient’ s age, comorbidities and functional status. MM is incurable. While the
Figure 6. Multiple lytic lesions in the humerus, scapula and ribs.
a visual analysis of cells in metaphase
disease course is varied, patients typ-
and can be used to identify macro-
ically undergo a therapy regimen,
performed in hospital and a patient’ s
anti-myeloma therapy is based
previously undetectable levels( mini-
scopic karyotype abnormalities on
which is( hopefully) followed by a
own stem cells are collected and then
around proteasome inhibitors and
mum sensitivity in the most sensitive
bone marrow samples. 17p deletions,
period of remission and then an even-
returned to them after high doses of
lenalidomide.
currently available flow cytometry
hypodiploidy and chromosome 13
tual relapse that requires the consid-
chemotherapy( that typically ablates
As treatments for MM have
techniques is 1 / 100,000 nucleated
deletions are abnormalities associated
eration of alternative therapies( see
the bone marrow). Patients then usu-
improved significantly over recent
cells) and has been shown to correlate
with high-risk disease. 8
figure 8).
ally receive maintenance chemother-
years, the importance of detecting
with overall survival. 9
Fluorescent in situ hybridisa-
Initial treatment usually includes
apy, and their response to treatment
deeper responses to treatment has
There are two other modalities that
tion( FISH), a cytogenetic technique,
corticosteroids, a proteasome inhib-
is graded based on bone marrow biop-
emerged. Minimal residual disease
are key to the overall management of
uses fluorescent probes that bind
itor( such as bortezomib) and if their
sies, serum free light chain analysis,
( MRD) and MRD-negative status can
symptomatic myeloma: first, the man-
to a specific sample of DNA. These
renal function allows, lenalidomide or
and SPE and immunofixation of the
now be assessed via next-generation
agement of bone disease and hyper-
probes are able to identify translo-
thalidomide. The standard of care for
paraprotein on both serum and urine.
flow cytometry or next-generation
calcaemia; and second, anti-infective
cations, amplifications and dele-
younger and fitter patients is an autol-
In‘ less fit’ patients in whom high-
sequencing on bone marrow sam-
prophylaxis.
tions in plasma cells. Translocations
ogous stem cell transplant follow-
dose therapy and an autologous stem
ples. These technologies can detect
Myeloma cells produce osteo-
t( 4; 14) and t( 14; 16), 17p deletion and
ing initial induction therapy. This is
cell transplant are inappropriate,
the presence of the malignant clone at
clast-activating factors while inhibiting