Multiple myeloma is a cancer of plasma cells that results in excessive proliferation of monoclonal proteins. It commonly causes lytic bone lesions, anemia, hypercalcemia and renal failure. Diagnosis involves blood and bone marrow tests detecting the monoclonal protein and plasma cell percentage. Staging systems include Durie-Salmon and International Staging System. Treatment involves disease-specific therapies like chemotherapy, steroids, stem cell transplantation and supportive care for complications. Bisphosphonates are the standard treatment for bone disease and fractures may require surgical stabilization.

1. Adi Surya Dharma
Pembimbing : dr . Mujaddid Idulhaq, Sp.OT (K)

2.  Multiple myeloma (MM) is characterized by
the neoplastic proliferation of a plasma cell
clone that produces a monoclonal
immunoglobulin.
 The plasma cell proliferation usually results
 in extensive skeletal involvement with lytic bone lesions
and/or severe osteoporosis with or without compression
fractures,
 hypercalcaemia,
 anaemia or extramedullary plasmacytomas
J. Blade, M. Teresa Cibeira, C. Ferna´ndez de Larrea & L. Rosin . Multiple myeloma in : Annals of Oncology 21 (Supplement 7): vii313–vii319, 2010

3.  Constitutes 1% of malignant diseases and
almost 15% of all haematological
malignancies.
 The incidence in blacks is twice that in
whites
 The peak of higher incidence is between 60
and 70 years of age.
Only 15% and 2% of patients are < 50 and 40
years

4. Myeloma cells
release RANK ligand (RANKL),
stimulating osteoclasts, and
dick-kopf 1 (DKK1), a
protein that inhibits
osteoblastic function
and leads to loss of
osteoblastic differentiation
and destruction of
osteoblast-lineage stem
cells, resulting in lytic bone
lesions

5.  Clinical presentation of multiple myeloma
ranges from asymptomatic, with incidental
discovery, to symptomatic
 The clinical manifestations of end-organ
damage that meets the criteria for the
diagnosis of MM consists of a group of
findings referred to as CRAB:
a. Hypercalcemia (serum calcium level greater than 0.25 mmol per L above the upper
limit of normal, or greater than 2.75 mmol per L, or greater than 11.0 mg per dL)
b. Renal insufficiency (creatinine level greater than 173 mmol per L or greater than 1.9
mg per dL)
c. Anemia (hemoglobin level of 2.0 gm per dL below the lower limit of normal or less than
10 gm per dL)
d. Bone lesions (lytic bony lesions or osteoporosis with compression fractures)

6. Include
 history
 physical examination
 the following baseline blood studies
and biological assessments to
differentiate symptomatic and
asymptomatic MM:
▪ a CBC with differential and platelet counts; blood urea
nitrogen (BUN);
▪ serum creatinine
▪ serum electrolytes
▪ serum calcium
▪ Albumin
▪ lactate dehydrogenase (LDH)

7.  Serum analysis also includes quantitative
immunoglobulin levels of different types of antibodies
(IgG, and IgM); serum protein electrophoresis (SPEP);
and serum immunofixation electrophoresis (SIFE) to
obtain more specific information about the type of
abnormal antibodies present and to determine the
extent of immunoparesis.
Electrophoresis results demonstrate a monoclonal
protein level (ie, M spike) that represents the antibody
produced by the tumor cells.
 The abnormal proteins found in urine (ie, Bence Jones)
are composed of the free light chains that are excreted
through the kidney.
 Radiography
 Bone marrow aspirate is evaluated to measure the
percentage of plasma cells.
 Biopsy is required in some cases, such as in the patient
with sus-pected plasmacytoma and when elec-
trophoresis is not obtained.

8. A. Plain radiographs : the standard of
care for evaluation of persons with
myeloma.
A survey of the appendicular skeleton,
spine, pelvis, and skull should be
performed in persons with suspected
myeloma
Lesions are not evident on plain
radiographs until approximately 50%
bone destruction has occurred.
Typical myeloma lesions are
small (average, 20 mm) and lytic, with
a sharp zone of transition and lack of
reactive bone.

10. B. CT
Helpful in defining
the extent of lytic
bone lesions that are
poorly visualized
radiographically.
C . Nuclear bone scan
Technetium-based bone
scans rely on an
osteoblastic response for
uptake of the
radiopharmaceutical
agent
Bone scan tends to be
unreliable, and the extent
of disease can be
underesti-mated
In general, lesions with
uptake on bone scan are
the result of a
complication of myeloma,
such as insufficiency or

11. FDG PET had sensitivity
of 92.7% in identifying
radiographically os-
teolytic lesions
D. MRI
 MRI appears to be more
sensitive and specific
than radiography in
identifying bone marrow
lesions, especially in the
pelvis and spine.
T1-weighted spin-echo
images, a lesion appears
as a hypointense area on
a background of
hyperintense marrow
T2-weighted spin-echo
se-quences reveal
hyperintense focal im-
ages relative to the

12.  Findings suggestive of
myeloma include :
 an expansile focal mass,
 multiple focal masses in
the appendicular
skeleton,
 diffuse marrow
involvement,
 multiple compression
fractures in the patient
with no known
malignancy.
 MRI also may be used to
monitor response to
treatment because it can
show reduction in or
resolution of lesions

13. J. Scharschmidt, Thomas MD, et all . Multiple Myeloma: Diagnosis and Orthopaedic Implications.JAAOS.

14. Anderson C. Kenneth, Multiple Myeloma in J Natl Compr Canc Netw2011;9:1146-1183Anderson C. Kenneth, Multiple Myeloma in J Natl Compr Canc Netw2011;9:1146-1183
DIAGNOSTIC CATEGORIESDIAGNOSTIC CATEGORIES
Based on the results of the clinical and laboratory evaluation,
patients categorized as :
a.Smoldering (asymptomatic) ,
Agreed i by the International Myeloma Working Group
(IMWG) for:
• low concentrations of M-protein (≥ 30 g/L) and/or
• bone marrow infiltration greater than or equal to 10% plasma cells, but
with no anemia, renal failure, hypercalcemia, or bone lesions.
b. Active (symptomatic) disease ;
Categorized according to stage, based on either
the Durie-Salmon staging system or the International
Staging System (ISS).

16.  In 2003, the original system was updated to
incorporate MRI findings and was renamed
Durie-Salmon PLUS.
a. stage I disease : presence of 0 - 4 focal
bone lesions and/or mild diffuse spine
disease on MRI
b. Stage II disease: presence of 5 - 20 focal
bone lesions and/or moderate diffuse spine
disease visible on MRI.
c. Stage III disease: >20 focal bone lesions
and/or severe diffuse spine disease is
visible on MRI

17. Robert A. Kyle, M.D. Clinical Course and Prognosis of Smoldering (Asymptomatic) Multiple Myeloma n engl j med 356;25 www.nejm.org june 21, 2007

18.  The treatment of myeloma comprises :
A. Disease-specific therapy
▪ For active disease
▪ Definitive therapy is required when the patient is symptomatic or when organ
dysfunction is present or impending.
B . Supportive care.
Seema Singhal* and Jayesh Mehta . Multiple myeloma. Clin J Am Soc Nephrol 1: 1322–1330, 2006.

19.  Comprises management of :
 hypercalcemia,
 skeletal complications,
 anemia,
 infections, and
 pain
Supportive Therapy

20.  Current standard approach consists of
 initial induction therapy,
 consolidation with high-dosage chemotherapy
and
autologous HSCT,
 maintenance therapy, and
 salvage therapy.

22.  Goals:
relieve disabling symptoms, and in
particular the severe bone pain,
thereby improving quality of life.
 Bisphosphonates become the standard
anti-osteolytic therapy for myeloma-
induced bone disease.

23.  Lytic disease on plain radiographs or imaging
studies:
Intravenous pamidronate 90 mg delivered
over at least 2 hours or zoledronic acid 4 mg
delivered over at least 15 minutes every 3 to 4
weeks is recommended.
Zervas Et al : 9.5-fold greater risk for the development of osteonecrosis of the
jaw with Zoledronic acid compared with pamidronate

24. Monitoring:
 Patients with pre-existing mild-to-moderate renal
impairment (estimated creatinine clearance, 30 to 60
mL/min) : a reduced dosage of zoledronic acid.
No changes in infusion time or interval are required.
Zoledronic acid is not recommended for use in severe
renal impairment .
 Pamidronate 90 mg administered over 4 to 6 hours
recommended for patients with extensive bone disease
and existing severe renal impairment (serum creatinine
level >3.0 mg/dL or an estimated creatinine clearance 30
mL/min).
 serum creatinine should be monitored before each dose

25.  intermittent evaluation (every 3 to 6 months) of all
patients receiving pamidronate or zoledronic acid
therapy for the presence of albuminuria. In patients
experiencing unexplained albuminuria (defined as >
500 mg/24 hours of urinary albumin), discontinuation
of the drug is advised until the renal problems are
resolved. These patients should be reassessed every 3 to
4 weeks (with a 24-hour urine collection for total protein
and urine protein electrophoresis), and pamidronate
should be reinstituted over a longer infusion time ( >4
hours) and at doses not to exceed 90 mg every 4 weeks
when the renal function returns to baseline.

26. Duration of therapy administered monthly for
a period 2 years. At 2 years, the physician
should seriously consider stopping
bisphosphonates in patients with responsive
or stable disease, but their further use is at
the discretion of the treating physician.
For those patients in whom bisphosphonates
were withdrawn after 2 years, the drug
should be resumed upon relapse with new-
onset skeletal-related events.

27.  Patients with solitary plasmacytoma or smoldering or
indolent myeloma without documented lytic bone
disease or with solitary plasmacytoma or smoldering
(asymptomatic) or indolent myeloma is not
recommended.
 Intravenous pamidronate or zoledronic acid is
recommended for patients with pain as a result of
osteolytic disease and as an adjunctive treatment for
patients receiving radiation therapy, analgesics, or
surgical intervention to stabilize fractures or impending
fractures.

28.  The orthopaedic surgeon may be consulted to
 performa biopsy for initial diagnosis,
is required in some cases, such as in the patient with
suspected plasmacytoma and when electrophoresis is
not obtained.
carefully because very vascular, and a risk of
substantial blood loss and also be taken into account
during preplanning for intramedullary or open
procedures.
 provide recommendations for nonsurgical care,
 perform prophylactic fixation of impending
fractures, or
 evaluate a painful bone lesion in a patient with known
myeloma to determine whether prophyactic surgical
stabilization is warranted.
Pain can be produced by the tumor itself (the lesion
frequently
responds to radiation therapy) or by mechanical
weakening bone

30.  Stabilize pathologic fractures in the patient
with myeloma bone disease.
▪ important consideration is a lesion that does not meet
criteria for surgical stabilization but is located in a
high-risk area in a patient for transplant, so an
aggressive surgical approach pre-transplant may be
considered.
▪ For impending fracture or a painful lesion that is
unresponsive to radiation therapy, stabilization surgery
is typically recommended when life expectancy is
>3 month
▪ When surgery is chosen, typically with
intramedullary fixation, to avoid creating new
stress risers in pathologic bone

31. Terima Kasih