1. 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 population / year
more frequent in elderly
modest male predominance

2. Multiple myeloma

3. Multiple Myeloma

4. Multiple Myeloma Clinical symptoms: bone pains, pathologic fractures
weakness and fatigue
serious infection
renal failure
bleeding diathesis

5. Multiple Myeloma Laboratory tests: ESR > 100
anaemia, thrombocytopenia
rouleaux in peripheral blood smears
marrow plasmocytosis > 10 %
hyperproteinemia
hypercalcemia
proteinuria

6. Multiple myeloma INITIAL DIAGNOSTIC WORKUP
2011

9. Diagnostic Criteria for Multiple Myeloma (old)
Major criteria
I. Plasmacytoma on tissue biopsy
II. Bone marrow plasma cell > 30%
III. Monoclonal M spike on electrophoresis IgG > 3,5g/dl,
IgA > 2g/dl, light chain > 1g/dl in 24h urine sample
Minor criteria
a. Bone marrow plasma cells 10-30%
b. M spike but less than above
c. Lytic bone lesions
d. Normal IgM < 50mg, IgA < 100mg, IgG < 600mg/dl

10. Diagnostic Criteria for Multiple Myeloma
Diagnosis:
I + b, I + c, I + d
II + b, II + c, II + d
III + a, III + c, I II + d
a + b + c, a +b + d

11. Multiple Myeloma

12. Diagnostic Criteria for Multiple Myeloma (present)
Plasmocytosis >= 10% and/or plazmocytoma infiltration
M protein
Myeloma related damage (CRAB)

13. Diagnostic Criteria for Multiple Myeloma (present)
C (Calcium) (> 2,75 mmol/l)
R (Renal Insufficiency) creatinine concentration >173 mmol/l (1,96 mg/dl)
A (Anemia) Hg <10 g/dl
B (Bone lesions)

14. Monoclonal gammopathy of undetermined significance ( MGUS)
M protein present, stable
levels of M protein: IgG < 3,0g IgA < 2g LC<1g/day
normal immunoglobulins - normal levels
marrow plasmacytosis < 10%
complete blood count - normal
no lytic bone lesions
no signs of disease

15. Smouldering multiple myeloma
M protein present, stable
levels of M protein: IgG  3,0g IgA  2g LC  1g/day
normal immunoglobulins - normal levels
marrow plasmacytosis  10%
complete blood count - normal
no lytic bone lesions
no signs of disease

16. Staging of Multiple Myeloma
Clinical staging (Salmon-Durie)
is based on level of haemoglobin, serum calcium, immunoglobulins and presence or not of lytic bone lesions
correlates with myeloma burden and prognosis
I. Low tumor mass
II. Intermediate tumor mass
III. High tumor mass
subclassification
A - creatinine < 2mg/dl
B - creatinine > 2mg/dl

17. ISS (International Staging System for multiple myeloma)
Stage
MOS (months) I
β2 microglobulin < 3,5 mg/l and albumins > 3,5 g/dl 62 II
No criteria for I and III 44
III
β2 mikroglobulin >5,5 mg/l 29

19. MM treatment Thalidomide TNF-α inhibitor
b-FGF and VEGF2 inhibitor (antiangiogenic factor)
Apoptosis promotion ( NF-κB )
Induktion of Th1 activity with production of IFN-γ i IL-2)

20. MM treatment MP („gold standard” )
Melfalan 9 mg/m2 po 1-4 day every 6 weeks
Prednison 60 mg/m2 po 1-4 day every 6 weeks
Up to 9 cycles
OR (CR+PR+MR) 47%
OS 32 months
Infections (3 i 4 NCI grade) 18%

21. MM treatment Bortesomib Reversible proteasoms’ inhibitor
NFκB inhibitor (promotes apoptosis)
registered for 2nd and 3rd line

23. Treatment of Multiple Myeloma
Event-free and overall survival times of 515 patients receiving autotransplants and a median follow-up of at least 5 years.

24. Treatment of Multiple Myeloma
New methods
Non-myeloablative therapy and allogeneic transplantation
Tandem transplants
Bortesomib (proteasome inhibitor)
Lenalidomide
Arsenic trioxide
Statins

25. Treatment of Multiple Myeloma
Supportive treatment
biphosphonates, calcitonin
recombinant erythropoietin
immunoglobulins
plasma exchange
radiation therapy

26. 2011

27. Disorder Associated with Monoclonal Protein
Neoplastic cell proliferation
multiple myeloma
solitary plasmacytoma
Waldenstrom macroglobulinemia
heavy chain disease
primary amyloidosis
Undetermined significance
monoclonal gammopathy of undetermined significance (MGUS)
Transient M protein
viral infection
post-valve replacement
Malignacy
bowel cancer, breast cancer
Immune dysregulation
AIDS, old age
Chronic inflamation