Plasma Cell Neoplasms
Plasma Cell Neoplasms
Plasma Cell Neoplasms
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Myeloma
• Cancer of plasma cells in the bone marrow
• AKA multiple myeloma, plasma cell myeloma, Kahler’s
disease
• Abnormal accumulation of myeloma cells in bone marrow:
• Disruption of normal bone marrow function (anemia, low white cell
count or platelet count)
• Destruction and invasion of bone and surrounding areas of bone
marrow involvement
• Production and release of monoclonal protein from
myeloma cells into the blood stream and/or into urine
• Reduction of normal immune function, reflected by reduced
levels of normal immunoglobulins and increased
susceptibility to infection.
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Monoclonal protein
• M-protein, M-spike, M-component,
Paraprotein, myeloma protein, protein spike
• Immunoglobulin or fragment of an Ig
• Myeloma Ig tend to
be abnormal, without
normal antibody function
• Can be used in lab to
determine myeloma
activity
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Increased production of abnormal Ig
• Excess monoclonal protein accumulation in blood
and/or urine
• Can stick to each other and/or blood components,
vessels- reducing blood flow and circulation
• Excess light chains (Bence Jones proteins)
• Abnormal properties:
– binding to normal blood clotting factors (bleeding,
clotting)
– binding to nerves (peripheral neuropathy)
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Definitions
• Monoclonal Gammopathy of Undetermined
Significance (MGUS)
– M-protein present but usually <3 g/dl
– No CRAB features or other indicators of active myeloma
– Bone marrow plasma cells <10%
• Asymptomatic or Smoldering Multiple Myeloma
– M-protein >3 and/or BMPC >10%
– No CRAB features or other indicators of active myeloma
• Active or Symptomatic Multiple Myeloma
– 1/> CRAB features and/or indicators of organ damage
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C alcium elevation
L ight chain ratio ≥100
R enal failure
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maging by MRI or PET >1 focal lesion
A nemia
B one disease
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Spectrum of tumor burden and activity
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Clinical features
• Symptoms
– Persistent or worsening tiredness
– Sudden and non-remitting pain
– Recurrent unexplained infections
• Signs
– Pain with movement and/or at night
– Tenderness/swelling of bone areas
– Swelling, shortness of breath or evidence of heart
or kidney failure
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Diagnosis
• Serum electrophoresis (M spike quantification)
• Serum immunofixation (M spike type)
• Serum free light chains
– Kappa, Lambda. Look at unit: mg/dl or mg/L
• Urine protein electrophoresis and immunofixation
• Serum LDH (risk status)
• Serum albumin + Serum beta2 microglobulin (staging)
• Bone marrow biopsy (risk status)
– Percent plasma cells
– FISH analysis
– Cytogenetics
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Staging at diagnosis
• ISS (2005) ISS I: Β2MG <3.5, alb ≥3.5
ISS II: everything else
– Serum β2 microglobulin
ISS III: Β2MG ≥5.5
– Serum albumin
• R-ISS (2015)
R-ISS I: ISS I, no FISH abn, nl LDH
– ISS
R-ISS II: everything else
– FISH R-ISS III: ISS III + (↑LDH or FISH abn)
• del17p +/-
• t(4;14) +/-
• t(14;16)
– LDH >ULN
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Treatment
• Induction chemotherapy
• Autologous transplant
• Allogeneic transplant
• Tandem transplant
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Induction therapies
• Lines of treatment (1 line = a particular combination).
• A line may be used for 1/> cycles
• Priming is not line of treatment (Cytoxan, Etoposide)
• Chemotherapy lines include combinations such as
– Bortezomib, Lenalidomide, Dexamethasome (VRD)
– Cytoxan, Bortezomib, Dexamethasone (CyBorD, VCD)
– Bortezomib, Dexamethasone (VD)
– Lenalidomide, Dexamethasone (RD)
– Other drugs: carfilzomib (K), pomalidomide , thalidomide, elotuzumab,
daratumumab, bendamustine, melphalan
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Response assessment(IMWG Response Criteria)
Category Criteria
Stringent complete response CR + normal FLC ratio and absence of clonal cells in
BM by IHC
CR (-) IF on sr/ur + disappearance of any soft tissue
plasmacytomas and <5% PC in BM
VGPR Sr/Ur M-protein on IF but not on EP or ≥90% ↓ in sr M
+ ur M <100 mg/24 h
PR ≥50% ↓ Sr M-protein + ↓ 24 h ur M-protein by ≥90%
or to <200 mg per 24 h
MR ≥25% but ≤49% ↓ Sr M-protein and ↓ Ur M-protein by
50-89%
Progressive ds ↑ of 25% from lowest confirmed response in 1/>
Sr M-protein (absolute increase ≥0.5)
Clinical relapse CRAB, new plasmacytomas or bone lesions,
hyperviscosity
Relapse from CR Reappearance of sr/ur M-protein by IF/EP or ≥5% of
plasma cells in BM, appearance of any sign of
progression
Kumar S et al. Lancet Oncol. 2016 Aug 15
Prognosis
• Incurable, but controllable
• Outcomes have continued to improve for MM
• Median survival
– ISS I ~12-15 years
– High risk ds ~2 years
• Multiple relapses and remissions
• Majority of patients die of myeloma
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Plasmacytoma
• Plasma cell neoplasm presenting as a single
lesion
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Solitary Bone Plasmacytoma
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Evaluation
• CBC, chemistries
• SPEP with immunofixation
• Free light chain assay
• 24 h UPEP with immunofixation
• Bone marrow biopsy
• Skeletal survey
• PET/CT or MRI of spine/pelvis
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SBP plus MGUS
• <10% clonal plasma cells in bone marrow
• Treated as SBP but have a higher risk of
progression to symptomatic myeloma
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Treatment
• Localized radiation to the tumor site
• Multiple plasmacytomas- treat as multiple
myeloma
• Follow up
– Highest risk of recurrence in first 4 years
– Devpt of multiple myeloma, local recurrence of
new plasmacytomas
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Solitary Extramedullary Plasmacytoma
• 80% occur in head & neck region (upper
aerodigestive tract)
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Treatment
• Ideal treatment would be 2-pronged
– Therapy directed to lower concentration of
precursor protein
– Therapy directed toward amyloid fibrils
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Treatment if transplant eligible
• Chemotherapy followed by autologous stem
cell transplant
• Direct autologous stem cell transplant
• Careful selection of patients as AL patients
are more fragile (high early mortality)
• High response rates and long term survivors
(?selection bias)
• Multidisciplinary supportive care
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Transplant outcomes (N=1536)
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