Plasma Cell Disorders Flashcards
What are the rates of progression from smouldering myeloma to symptomatic myeloma and what are the risk factors for progression?
o 10% per year for the first 5 years following diagnosis, 3% per year over the next 5 years then 1% thereafter.
o Higher risk with t(4;14), del(17p) and gain 1q.
o Both plasma cells ≥10% and paraprotein ≥30g/L
o >95% of plasma cells in BM with an abnormal immunophenotype
o Abnormal serum free light chain ratio
o Immunosuppression of uninvolved immunoglobulins.
o High plasma cell Ki67/ proliferation rate
Rates are lower with light chain only multiple myeloma
What are the diagnostic criteria for non-IgM MGUS?
Serum monoclonal antibody (non-IgM) <30g/L
Clonal plasma cells <10% in the BM
Absence of symptoms or end organ damage
What is the definition of smouldering multiple myeloma
Serum monoclonal antibody ≥30g/L OR Clonal plasma cells 10-60% AND Absence of myeloma defining events or amyloidosis
List the myeloma defining events (as per the IMWG)
1) End organ damage that can be attributed to the underlying plasma cell disorder
- CRAB criteria
2) Clonal bone marrow population ≥60%
3) Involved: uninvolved SFLC ratio ≥100 (involved FLC must be ≥100mg/L)
4) >1 focal lesion on MRI imaging that is at least 5mm in size
What is the definition of light chain MGUS?
- Elevated involved SFLC
- Abnormal SFLC ratio
- No immunoglobulin heavy chain on immunofixation
- Malignant plasma cells <10% in BM
- Absence of end organ damage
- Urinary monoclonal protein <500mg/ 24hrs
What is the difference between solitary plasmacytoma and solitary plasmacytoma with minimal bone marrow involvement?
- Solitary plasmacytoma: no clonal plasma cells in the BM
- Solitary plasmacytoma with minimal bone marrow involvement: <10% clonal plasma cells in the BM
The presence of non-CRAB myeloma defining events is associated with what % progression to symptomatic disease?
80%
As per the IMWG what should the minimum FISH panel include?
- The high risk markers: t(4;14), t(14;16), del(17p)
- More comprehensive panel includes t(11;14), del 13, ploidy category, chromosome 1 abnormalities
List the primary molecular cytogenetic subgroups of multiple myeloma
- Hyperdiploid
- Non-hyperdiploid
o CCND translocations
t(11;14), t(6;14)
o NSD2/ MMSET translocation
t(4;14)
o MAF translocation
t(14;16)
t(14;20)
- Unclassified
List the poor risk cytogenetic markers in MM
- t(4;14) (adverse risk may be overcome in the bortezomib era)
- t(14;16)
- t(14;20)
- Gain 1q.
- del17(p)
List the poor prognostic factors in MM
Clinical
- Age
- ECOG
Lab
- Elevated B2M (>5.5)
- Elevated LDH
- Serum albumin <35
- Renal impairment
- High plasma cell Ki67
- Circulating plasma cells
Molecular
- Presence of high risk cytogenetic markers
(particularly t(4;14), t(14;16), t(14;20), gain 1q, del 17(p))
What is the definition of a CR and sCR in myeloma?
- Negative immunofixation of urine and serum
- Disappearance of any soft tissue plasmacytomas
- <5% BM plasma cells
sCR as above plus
- Normal SFLC ratio
- Absence of clonal plasma cells on flow cytometry
What is the definition of a VGPR in myeloma?
- Serum and urine M band detectable on immunofixation but not electrophoresis
- ≥90% reduction in paraprotein plus urine M protein <100mg per 24hrs
What are some of the goals of MRD assessment?
- Provide objective methodology to establish a deeper remission status
- Refine outcome prediction
- Inform post-remission treatment
- Identify impending relapse and enable early intervention
- Serve as a surrogate end point to accelerate drug testing and approval.
What is the definition of “MRD negative” as per the most recent IMWG recommendations?
Absence of clonal plasma cells by flow cytometry or sequencing based techniques with a minimum sensitivity of 10^5
