MULTIPLE MYELOMA

DIANA PARAMITA
Multistep molecular pathogenesis of MM
Germinal Intra- Extra-
MM
Center MGUS medullary medullary
Cell Line
B cell MM MM

Primary Ig translocations
cyclin D1 or D3
FGFR3 & MMSET
c-maf
others
Karyotypic instability
13q deletion

Somatic mutations
N-ras, K-ras, FGFR3
Secondary Ig translocations
c-myc
others
Lymphoproliferative Disorders Commonly
Associated with a Monoclonal
Gammopathy

Monoclonal gammopathy of undetermined

significance (MGUS)
Multiple myeloma
Waldenstroms macroglobulinemia
Amyloidosis
Multiple Myeloma

Definition:
B-cell malignancy characterised by abnormal
proliferation of plasma cells able to produce a monoclonal
immunoglobulin ( M protein )
Incidence:
3 - 9 cases per 100000 population / year
more frequent in elderly
modest male predominance
Malignant Plasma Cells
Myeloma cells produce substances that attack
bone --producing-> pain, fractures, hypercalcemia!
Diagnostic Criteria for Multiple
Myeloma
u Major criteria
I. Bone marrow plasmacytosis > 30%
II. Histologic diagnosis of plasmacytoma
III. Serum paraprotein IgG > 30 g/L or IgA > 20 g/L
u Minor criteria
a. Bone marrow plasmacytosis 10-30%
b. Serum paraprotein less than major criteria
c. Osteolytic lesion
d. Hypogammaglobulinemia

u Two major criteria

u One major criteria and one minor criteria
u Minor criteria a + b and one other
DIAGNOSTIC CRITERIA
(International Myeloma Working Group 2003)

Symptomatic Myeloma
1. Clonal plasma cells >10% on BM biopsy
2. Monoclonal protein in serum or urine
3. Evidence of end organ damage
Hypercalcemia
Renal insufficiency
Anemia (Hb <10 g/dL)
Bone lesions (lytic lesions or osteoporosis)
Infection
Amyloidosis
Hyperviscocity syndrome
DIAGNOSTIC CRITERIA
(International Myeloma Working Group 2003)

Symptomatic Myeloma
1. Clonal plasma cells >10% on BM biopsy
2. Monoclonal protein in serum or urine
3. Evidence of end organ damage
Hypercalcemia
Renal insufficiency
Anemia (Hb <10 g/dL)
Bone lesions (lytic lesions or osteoporosis)
Infection
Amyloidosis
Hyperviscocity syndrome
DIAGNOSTIC CRITERIA
(International Myeloma Working Group 2003)

Symptomatic Myeloma
1. Clonal plasma cells >10% on BM biopsy
2. Monoclonal protein in serum or urine
3. Evidence of end organ damage
Hypercalcemia
Renal insufficiency
Anemia (Hb <10 g/dL)
Bone lesions (lytic lesions or osteoporosis)
Infection
Amyloidosis
Hyperviscocity syndrome
Pemeriksaan laboratorium
untuk diagnostik (MM working group 2008)
Darah lengkap dengan hitung jenis
Morfologi darah tepi
Urine lengkap (termasuk silinder) dengan skrining
protein Bence Jones
Bila pasien anemi :
Kadar besi serum
TIBC
Feritin
Reticulocyte index
Pemeriksaan laboratorium
untuk diagnostik (MM working group
2008)
Kimia:
Kalsium
LDH
Kreatinin
Elektroforesis protein serum dan urine 24 jam, imunofiksasi serum dan
urine 24 jam
Imunoglobulin kuantitatif (nephelometry):
Ig G, Ig A
Aspirasi sumsum tulang:
Morfologi
Immunophenotyping
Sitogenetik, FISH
Beta-2 microglobulin
Pemeriksaan laboratorium untuk
diagnostik pada keadaan tertentu

C-reactive protein
Serum free light chain assay (belum dapat
dilakukan)
Viskositas serum

(MM working group 2008)

Pemeriksaan laboratorium untuk evaluasi
respon terapi

Elektroforesis protein serum dan urine 24

jam, imunofiksasi serum dan urine 24 jam
Aspirasi sumsum tulang
Serum free light chain assay (belum dapat
dilakukan)

(MM working group 2008)

IgA lambda gammopathy
 Mayor criteria of diagnostic
1.Kriteria Mayor.
1a. Sitologi aspirat BMP hitung jenis sel plasma dan atau sel
myeloma > 30%
1b. Histopatologi biopsi tulang dan atau jaringan lunak di
ketemukan Plasmositoma
1c. Monoclonal gammopati pada elektroforesis protein
plasma, elektroforesis urin, atau dijumpai protein Bence
Jones (> 1g/24jam).
 Minor criteria of diagnostic
2. Kriteria minor.
2a. Sitologi aspirat BMP hitung jenis sel plasma dan atau sel
myeloma > 10%.
2b. Adanya monoklonal gammopati pada immunoelektroforesis
IgG > 6g/L atau IgM > 0,5g/L atau IgA > 0,2 g/L
2c. Multipel Lesi osteolitik (punched out) pada bone survey.
Soliter Lesi osteolitik (punched out), atau lesi osteoporosis
generalisata dapat di pakai sebagai kriteria diagnostik jika
pada sitologi aspirat BMP hitung jenis sel plasma dan atau sel
myeloma di jumpai 30%.
2d. Hitung jenis lekosit darah tepi (in duplo) di jumpai sel plasma
dan atau sel myeloma
 Kriteria diagnosis

I. 1a dan 1b (Nonsecretoric), atau

1a dan 1c, atau
1b dan 1c.
II. 1a dengan salah satu dari 2b, 2c, dan 2d.
III. 1b dengan salah satu dari 2a, 2b, 2c, dan 2d.
IV. 1c dengan salah satu dari 2a, 2c, dan 2d.
 Stage 1 Stage 2/3
Fraktur patologis
Lesi soliter (extra medular)

Melfalan + Prednison
Radioterapi (Kontrol lokal)

Progresif
Stable disease Indikasi VAD
Remisi sebagian
Kontraindikasi

VAD (3 siklus) YA/ADA

Progresif
(Remisi sempurna) Stable disease
Remisi sebagian

Maintenance
MP (Intron) (Remisi sempurna) CHOP

Progresif
Stable disease
Remisi sebagian

Progresive kemoterapi
PBSC Rescue
 Therapeutics response
Respons sitologi aspirat BMP:
Remisi komplit:
Hitung sel plasma < 5% selama 3 bulan
berturut-turut
Remisi partial:
Respons hitung sel plasma > 50%
Remisi minimal:
Respons hitung sel plasma 25-50%
D Sel plasma
Respons = X 100%
Sel plasma praterapi
 VCMP-VACP alternate protocol
every 3 weekly
VCMP Dosis day
Vinkristin 2 mg in 50 mL NS iv drip 30 1
Cyclofosfamid 500 mg/m2 in 100 mL NS iv drip 60 1
Melphalan 6 mg/m2/hari/oral 1-5
Prednison 100 mg/day/oral 1-5

VACP Dosis day

Vinkristin 2 mg in 50 mL NS iv drip 30 1
Doxorubicin 30 mg/m2 in 50 mL NS iv drip 30 1
CCNU* 100 mg/m2/oral 1
Prednison 100 mg/day/oral 1-5

*Lomustine (CeeNU) Cap 10, 40, 100 mg

 VAD and CHOP protocol in
MM
VAD Dosis di berikan hari ke
Vinkristin 0,4 mg/hari/iv bolus 1-4
Doxorubicin 9 mg/m2/iv bolus 1-4
Dexamethason 40 mg/day/oral or iv 1-4, 9-12, 17-20

CHOP Dosis di berikan hari ke

Vinkristin 2 mg in 50 mL NS iv drip 30 1
Doxorubicin 40 mg/m2 in 50 mL NS iv drip 30 1
Cyclofosfamid 500 mg/m2 in 100 mL NS iv drip 60 1
Prednison 100 mg/day/oral 1-5