Multiple myeloma
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Transcript Multiple myeloma
PLASMA CELL DYSCRASIAS
CLASSIFICATION
• Monoclonal gammopathy of uncertain
significance (MGUS)
Idiopathic
Associated with other diseases (autoimmune,
infectious, non-heme cancer, etc)
• Plasma cell or lymphoid malignancy
Waldenstrom's macroglobulinemia
Other lymphoproliferative disorders
Smoldering multiple myeloma
Multiple myeloma
MOLECULAR PATHOGENESIS OF MYELOMA
Lancet 2004;363:875
MULTIPLE MYELOMA
Definition
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Increased numbers of abnormal or immature plasma cells in
the bone marrow, or localized plasmacytoma
Monoclonal protein in blood or urine
Some patients are nonsecretors
Lytic bone lesions
Not all patients have lytic bone disease
MULTIPLE MYELOMA
EPIDEMIOLOGY
• Incidence in US approx 3 cases/100,000/yr
• 98% of cases > 40 yrs old
• Risk factors:
genetic
radiation exposure
? chemical exposure
MULTIPLE MYELOMA
Serum and urine protein electrophoresis
Monoclonal IgG
Serum
Urine
Free light chain
Multiple myeloma (IgG kappa)
IgG 2080
Anemia, leukopenia
Lytic bone lesions
10% marrow plasma cells
Multiple myeloma (IgA)
IgA 1010 (nl 70-140)
IgG 165 (nl 695-2190)
IgM 14 (nl 60-265)
Anemia, thrombocytopenia
16% marrow plasma cells
MGUS
Ifix: monoclonal IgG kappa
No proteinuria
IgA 234 (50-540)
IgG 1840 (600-1600)
IgM 85 (40-250)
Normal CBC
Waldenstrom macroglobulinemia with
hyperviscosity syndrome
Anemia, fatigue, retinopathy, bleeding disorder
IgA 125 (70-440)
IgG 724 (695-2190)
IgM 5130 (60-265)
Serum viscosity 3.6
Marrow: <5% plasmacytoid B-lymphocytes
Waldenstrom macroglobulinemia
Mild fatigue
IgM 8460, serum viscosity 2.7
Hgb 12, WBC 3700, platelets 143,000
Marrow: 50% plasmacytoid B-lymphocytes
Kappa light chain myeloma with cardiac
amyloidosis
Serum (hypogammaglobulinemia)
Urine (kappa light chain)
Always check the urine!
MULTIPLE MYELOMA – BONE MARROW ASPIRATE
MYELOMA CYTOGENETICS
t(4;14)
del (13)
Lancet 2004;363:875
MULTIPLE MYELOMA
DIAGNOSIS
• Monoclonal paraprotein
Intact immunoglobulin in serum (SPEP)
Light chains in serum or urine (IEP)
• Marrow plasmacytosis (> 20% - may be patchy)
• Lytic bone lesions
• Plasmacytoma
MULTIPLE MYELOMA
CLINICAL MANIFESTATIONS
• Anemia progressing to pancytopenia
• Bone pain/destruction
• Hypercalcemia
• Humoral immune defect
• Local effects of plasmacytomas
• Systemic effects of paraprotein
MONOCLONAL GAMMOPATHY
COMPLICATIONS
• Hyperviscosity (IgM >> IgA > IgG)
• Renal dysfunction (light chains)
Glomerular
Tubular
Neuropathy
Other organ damage (rare)
Cryoglobulinemia (types I and II)
Amyloidosis
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MULTIPLE MYELOMA
Cast nephropathy
CRYOGLOBULINEMIA IN IgM GAMMOPATHY
Brit J Haematol 2004; 124:565
MULTIPLE MYELOMA
Demographics
Mayo Clin Proc 2003;78:21
MULTIPLE MYELOMA
Presenting features (1027 pts)
Mayo Clin Proc 2003;78:21
Bone pain
58%
Fatigue
32%
Weight loss
24%
Paresthesias
5%
Fever
0.7%
ECOG PS >2
10%
MULTIPLE MYELOMA
Preexisting conditions and risk factors
Mayo Clin Proc 2003;78:21
Cancer in 1st degree
relative
42%
Myeloma in 1st degree
relative
2%
Hx of plasma cell
proliferative disorder
34%
MULTIPLE MYELOMA
Pre-existing plasma cell disorders
Mayo Clin Proc 2003;78:21
MULTIPLE MYELOMA
Physical findings
Mayo Clin Proc 2003;78:21
Palpable liver
4%
Palpable spleen
1%
Lymphadenopathy
1%
MULTIPLE MYELOMA
Hematologic findings at presentation
Mayo Clin Proc 2003;78:21
Hgb < 12
73%
Hgb < 8
7%
ESR > 20
84%
ESR > 100
33%
WBC < 4000
20%
WBC < 2000
1%
Plts < 100K
5%
Plts > 500K
2%
MULTIPLE MYELOMA
Laboratory findings
Mayo Clin Proc 2003;78:21
MULTIPLE MYELOMA
Serum and urine proteins
Mayo Clin Proc 2003;78:21
Monoclonal band on SPEP in 82%
3% non-secretory at presentation
MULTIPLE MYELOMA
Types of monoclonal proteins
Mayo Clin Proc 2003;78:21
MULTIPLE MYELOMA
Radiographic findings at presentation
Mayo Clin Proc 2003;78:21
MULTIPLE MYELOMA
Survival
Mayo Clin Proc 2003;78:21
MULTIPLE MYELOMA
Prognostic factors
Mayo Clin Proc 2003;78:21
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* Most important factors in multivariate analysis
*Adapted from Greipp et al, Blood 2003;102:190a
Adverse cytogenetics in myeloma
del13 or del13q
t(4;14
del17p
MULTIPLE MYELOMA
INDICATIONS FOR TREATMENT
• Symptomatic disease
• Bone destruction
• Anemia
• Organ dysfunction
• Hypercalcemia
• Increasing paraprotein
microglobulin level
or ß2-
Treatment mnemonic
• Calcium increased
• Renal dysfunction
• Anemia
• Bone lesions
MULTIPLE MYELOMA
TREATMENT
• Initial treatment:
– Thalidomide or lenalidomide + dexamethasone
– Bortezomib + dexamethasone
– Bortezomib + lenalidomide + dexamethasone
– Melphalan + prednisone + lenalidomide/thalidomide
• Autologous SCT prolongs survival
• Refractory disease:
– High dose cyclophosphamide
– Platinum-based regimen
• Bisphosphonates as adjunctive Rx
• Allogeneic transplant role?
Overall and progressionfree survival in multiple
myeloma: standard
chemotherapy vs highdose chemotherapy with
stem cell rescue
NEJM 2003;348:1875
Blood 2010;116:679-686
N Engl J Med 1996;334:488-93
Lancet 2004;363:875
How do thalidomide & related drugs work?
Science 2014;343:256