Multiple Myeloma
Multiple Myeloma is a treatable but incurable blood cancer that occurs when there is an overproduction of clonal plasma cells in the bone marrow. This overproduction impairs normal hematopoiesis, which can lead to bone fractures, anemia and renal dysfunction.1
Diagnosis is confirmed based on the SLiM-CRAB criteria 2:
- Sixty percent or more clonal bone marrow plasma cells*
- Involved/uninvolved serum free light chain ratio ≥ 100
- MRI with >1 focal lesions ‡
- Calcium elevation (6 %)
- Renal insufficiency (29 %)
- Anemia (57 %)
- Bone lesions (68 %)
* Clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence.
Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used.
† These values are based on the serum Freelite assay. The involved free light chain must be ≥100 mg/L.
‡ Each focal lesion must be 5 mm or more in size.
MRI = magnetic resonance imaging.
Multiple Myeloma and genetic abnormalities
The disease is characterized by a large spectrum of chromosomal abnormalities. Some of the most common abnormalities among this genetic complexity include IgH translocations which emerge when normal plasma cells transition to a clonal pre-malignant state. 3,4
Knowing a patient’s disease-specific mutations may help in determining disease stage, prognosis, and response to disease management.
Adapted from Rajan AM, Rajkumar SV. Blood Cancer J. 2015;5(10):e365
Despite improved trends in survival, there are Multiple Myeloma subtypes based on these cytogenetic prognostic markers that may have varying outcomes. That’s why cytogenetic testing is recommended for appropriate staging and risk stratification. 1,3
IgH = immunoglobulin heavy-chain gene
MGUS = monoclonal gammopathy of undetermined significance;
SMM = smoldering multiple myeloma.
Prevalence and risk
FISH helps identify cytogenetic abnormalities in Multiple Myeloma 3,5
Comprehensive FISH testing enables accurate stratification of individuals with newly diagnosed Multiple Myeloma into risk groups for prognosis and selection of therapy. 1,3,6,7
Over 90% of the translocations observed in all Multiple Myeloma cases involve chromosome 14. Most recurrent translocations involving chromosome 14 are regarded as primary cytogenetic events that initiate tumor development. 4
IgH translocations are observed in 50% - 70% of all Multiple Myeloma cases 4
t(11;14) is the most common translocation, this aberration can be identified early and is stable throughout disease progression 8
Prognostic implications of IgH translocations 9
Mayo Clinic mSMART 3.0 risk stratification guidelines classify the following translocations* as either standard or high-risk events:
* this is not an exhaustive list.
Standard risk is defined as having an indolent course of disease and lengthy survival, while high-risk patients experience a more aggressive course and shorter survival.
Clinical Practice Guidelines 10,11
Clinical Practice guidelines for diagnosis, treatment and follow-up for Multiple Myeloma recommend karyotype and FISH for detection of del17p, t(4;14), t(14;16), ampl 1q/ gain 1q, t(11;14)* and t (14;20)#
* in S3-guideline only recommended optional, # not recommended in EHA-ESMO guidelines but in S3-guidelines
FISH = fluorescence in situ hybridization.
Comprehensive FISH testing = plasma cell enrichment prior to FISH
Plasma cell enrichment
In Multiple Myeloma, precise detection of cytogenetic abnormalities matters. That’s why it’s important to advocate for plasma cell enrichment prior to a FISH test for every patient (=comprehensive FISH testing).
Plasma cell enrichment increases FISH sensitivity and accuracy for cytogenetic abnormalities in Multiple Myeloma patients 5,12,13
- The accuracy of FISH results may be challenged by the low percentage of plasma cells in the bone marrow aspirate and by poor growth of plasma cells ex vivo.
- Plasma cell enrichment prior to FISH helps enhance detection of cytogenetic abnormalities, which may help improve appropriate stratification of a patient’s risk with a plasma cell neoplasm. 1,5,7
For these reasons, it is important that plasma cell enrichment is performed prior to FISH testing.
Together with FISH testing, plasma cell enrichment of the bone marrow sample can improve detection of cytogenetic abnormalities by almost 3x 7
Plasma cell enrichment is recommended prior to FISH testing by current guidelines:
- The International Myeloma Working Group 6
- EHA-ESMO Clinical Practice Guidelines 10
- S3-Guidelines 11
FISH = fluorescence in situ hybridization.
Comprehensive FISH testing = plasma cell enrichment prior to FISH
Personalised Patient Care
Comprehensive cytogenetic testing can foster personalised patient care
Personalised medicine has the potential to transform medical interventions by providing effective tailored therapeutic strategies based on the genomic, epigenomic, and proteomic profiles of the individual.
Improving the sensitivity of FISH will provide more information about patient characteristics and may provide additional information about cytogenetic abnormalities, which may assist doctors in providing personalised care. 1,7
Personalised medicine enables hematologists to stratify individuals into subpopulations that vary in their response to a therapeutic agent for their specific disease.
Download summary
