Transcript Multiple myeloma

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
Multiple myeloma
Multiple Myeloma
Multiple Myeloma
Clinical symptoms:
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bone pains, pathologic fractures
weakness and fatigue
serious infection
renal failure
bleeding diathesis
Multiple Myeloma
Laboratory tests:
• ESR > 100
• anaemia, thrombocytopenia
• rouleaux in peripheral blood smears
• marrow plasmocytosis > 10 %
• hyperproteinemia
• hypercalcemia
• proteinuria
Multiple myeloma
INITIAL DIAGNOSTIC WORKUP
2011
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
Diagnostic Criteria for Multiple Myeloma
Diagnosis:
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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
Multiple Myeloma
Diagnostic Criteria for Multiple
Myeloma (present)
–Plasmocytosis >= 10% and/or
plazmocytoma infiltration
–M protein
– Myeloma related damage
(CRAB)
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)
Monoclonal gammopathy of undetermined
significance ( MGUS)
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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
Smouldering multiple myeloma
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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
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
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
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III
β2 mikroglobulin >5,5 mg/l
29
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)
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%
MM treatment
• Bortesomib
– Reversible proteasoms’ inhibitor
– NFκB inhibitor (promotes apoptosis)
– registered for 2nd and 3rd line
Multiple myeloma diagnosis
Pt qualified for auto PBSCT
(younger than 65)
Older than 65
or not qualified for PBSCT
Melphalan
Prednisone
Thalidomide
Thalidomide
Dexamethasone
Thalidomide as sustaining
treatment ?
Mobilization chemotherapy and
collection of stemm cells
Melphalan 200 mg and PBSCT
Thalidomide as sustaining
treatment ?
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.
Treatment of Multiple Myeloma
• New methods
– Non-myeloablative therapy and allogeneic
transplantation
– Tandem transplants
– Bortesomib (proteasome inhibitor)
– Lenalidomide
– Arsenic trioxide
– Statins
Treatment of Multiple Myeloma
• Supportive treatment
– biphosphonates, calcitonin
– recombinant erythropoietin
– immunoglobulins
– plasma exchange
– radiation therapy
2011
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