Multiple Myeloma

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 Epidemiology

1% Of all malignant diseases.

Annual incidence: 3-4/100 000.
In the US 16,000 people are diagnosed and
more than 11,000 die with MM each year
Age:
- Median age: 65y.
- The diagnosis of MM in a patient <
30y should only be made after careful
evaluation of all data.
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 Epidemiology

• Incurable in almost all patients

• Median survival from diagnosis is 4-5

years

• More frequent in men than women

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 Multiple Myeloma
• Malignancy of plasma cells
•Plasma cells >10% of bone marrow

Hallmarks
• Presence of monoclonal protein
• Anemia
• Renal failure
• Bone destruction (lytic bone lesions)
• Hypercalcemia
• Increased risk of infection
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 Multiple Myeloma
Clinical Picture

Paraprotein

TRIAD

Osteolytic Bone ++ Myeloma

Lesions cells in BM
MULTIPLE MYELOMA: Clinical Picture
MM

M o n o c lo n a l M a rro w Im m u n e
P r o te in In filtr a tio n D e fic ie n c y

Renal H y p e r v is c o s ity A m y lo id o s is A n a e m ia R e le a s e o f In fe c tio n s

F a ilu r e C y to k in e s

LL 6

Bone
D e s tr u c tio n

Bone H y p e r c a lc a e m ia
P a in s
 Symptoms
Bone pain
Tumor release of IL-6 (osteoclast
activating factor), causing lytic bone lesions

Infection
due to low Antibody production

Renal failure
Commonly due to hypercalcemia, Bence
Jones protein tubular damage, recurrent
pyelonephritis
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 Symptoms
Normocytic normochromic anemia

Weakness and fatigue

Confusion

Headache and retinopathy due to blood

hyperviscosity

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 Multiple Myeloma: Lab investigation

ESR: very high.

Serum protein electrophoresis: M-band.

Immunofixation or immunoelectrophoresis:

are confirmatory studies to define M- protein

heavy and light chain classes.
Multiple Myeloma: Lab investigation

Serum Ca: often .

Serum creatinine: often .
Anaemia (not obligatory): (rouleaux formation

of RBCs).
In uninvolved immunoglobulins.
+BJP in 24 hr urine collection (monoclonal light

chains). www.MansFans.com
 Multiple Myeloma

BM PICTURE:
(Aspirate & Trephine Biopsy)

• >10 % myeloma cells..

• More basophilic cytoplasm.
• Increased mitotic figures or multiple nuclei.
• Coarse chromatin.
• Plasma cell nests.
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 Multiple Myeloma

RADIODIAGNOSIS:
Radiological survey of the entire skeleton:
is mandatory.
MRI: is superior to CT for screening the vertebral column for
osteolytic lesions.
Bone scan: is not indicated (cold lesions).
REMEMBER!!
Iodine-containing contrast media may cause acute renal failure in
case of paraproteinaemia.
Lateral skull x-ray with typical findings of MM
Typical lesion in a tibia
 Multiple Myeloma

Criteria for Diagnosis:

(At least 1 major + 1 minor or 3 minors)

•Major Criteria:
(1) Plasmacytoma on tissue biopsy
(2) Marrow plasmacytosis > 30 %.
(3) Monoclonal protein:
Ig G > 3.5 g / dl.
Ig A > 2 g / dl.
BJP > 1 g / 24 hr.
 Multiple Myeloma

Criteria for Diagnosis:

Minor Criteria:
(1) Marrow plasmacytosis 10-29 %.
(2) Monoclonal protein present but
less than the above levels
(3) Lytic bone lesions
(4) Decrease in uninvolved Ig:
Ig M < 50 mg / dl.
Ig A < 100 mg / dl.
Ig G < 600 mg / dl.

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 Multiple Myeloma

Prognostic Factors

(1) Staging
(2) β-2 microglobulin
(3) CRP
(4) Cytogenetics
(5) LDH

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 Treatment of MM
Criteria of Response:
CR:
•No M-band in serum or urine on electrophoresis.
•BJP < 200 mg/24 hrs
•Plasma cells in BM < 5%

N.B. Immunofixation in serum and urine may still be positive.

VG PR:
•Decrease of M-band or light chains > 90 %.
•Plasma cells in BM < 10%
 Treatment of MM
Criteria of Response:
PR:
Decrease of M-band or light chains in
urine > 50 %.
Minimal Response (MR):
Decrease of M-band or light chains in
urine > 25 %.
No Change (NC):
No change in any parameter.
 Treatment of MM

Criteria of Response:
Progressive Disease(PD):
• Increase in M-band or light chains in
urine > 25 %.
• Development of new osteolytic
lesions.
• Newly developed hypercalcaemia.
Primary Resistance:
Response rate < 25 % after at least 4
full-dose treatment cycles.
Multiple Myeloma

Main Causes of Death:

• Uncontrolled infections 35%

• Renal failure 20%
• Bleeding 20%
• Secondary leukaemia 5%
 T R E A T M E N T P L A N IN M M
P a tie n ts > 6 0 y r s

A s y m p to m a tic S y m p to m a tic o r P D

N o tre a tm e n t M P till C R o r
M ax. R esponse

P r o g r e s s io n < 6 m o n th s P r o g r e s s io n > 6 m o n th s

VAD R epeat M P

PD PD

2 n d lin e VAD
 T R E A T M E N T P L A N IN M M
P a tie n ts < 6 0 y r s o f A g e

3 c o u rs e s o f V A D

C R PR
H L A -T y p in g A n o th e r
3 c o u rs e s o f V A D

N o H L A - Id e n t ic a l H L A - Id e n t ic a l C R
S ib lin g S ib lin g

AB M T M in i-T r a n s p la n t
TREATM ENT PLAN
IN M M
P a tie n ts w ith M in im a l R e s p o n s e

> 6 0 yrs < 6 0 y rs

VAD S e c o n d L in e
 Chemotherapy of MM

First line:
MP •Melphalan 8 mg/m2 P.O. day 1-4
(0.25mg\Kg\day X 4 days)
•Prednisone 60 mg/m2 P.O. day 1-4
Repeat every 4 weeks
VAD •VCR 0.4 mg C.I. day 1-4
•Adriamycin 9 mg/ m2 C.I. day 1-4
•Dexamethasone 40 mg P.O. day 1-4 & 9-12
(& day 17-20 in cycle 1 only)
Repeat every 3 weeks
 Chemotherapy of MM

Second line:
High dose dexamethasone:
40 mg I.V. day 1-4, 9-12,19-21.
DCEP •Dexamethasone 40 mg I.V. day 1-4
•Cyclophosphamide 300 mg/ m2 C.I. day 1-4
•Etoposide 30 mg/ m2 C.I. day 1-4
•Platinol 15 mg/ m2 C.I. day 1-4
CEP to be mixed together in 1L normal saline.
Not compatible with Mg or Kcl
Treatment of MM

Radiotherapy:
Indications:
• Big osteolytic lesions.
• Significant osteolytic lesions in
weight-bearing bone (for fear
of pathological fracture).
• Cord compression.
• Extramedullary plasmacytoma.