Methods for detection of MRD in multiple myeloma
Increasingly sensitive techniques are available for the detection and quantification of
MRD in multiple myeloma. Each technique offers advantages and inherent limitations that
might differentially affect their use and interpretation of the findings.72
Features of MRD detection methods15,69,72
| Method |
Process |
Applicability |
Sensitivity |
Important considerations |
MFC
(≥ 8 color) |
Differentiates between normal and abnormal plasma cells
through detection of cell-surface marker expression |
-100% |
10-5-10-6 |
- Widely applicable and available
- Hours
- Relatively inexpensive
- Clonal heterogeneity undetectable
- Standardized by the EuroFlow consortium
- Requires bone marrow aspirate
- Fresh sample necessary
- Does not require baseline sample
|
| ASO-PCR |
Analysis of VDJ heavy chain regions for detection of
myeloma-specific Ig rearrangements |
60%-70% |
10-5-10-6 |
- Intermediate applicability and availability
- Days to weeks
- More expensive
- Clonal heterogeneity undetectable
- Standardized (EuroMRD)
- Requires bone marrow aspirate
- Fresh sample not necessary
- Patient-specific primers necessary
- Requires baseline sample
|
| NGS |
Use of high throughput sequencing to detect clonal Ig VDJ
gene rearrangements |
-90% |
10-6 |
- Limited availability
- One week or more
- Expensive, but costs decreasing
- Limited clonal heterogeneity detected
- Not yet standardized
- Bone marrow aspirate or peripheral blood sample acceptable
- Fresh sample not necessary
- Requires baseline sample or stored sample from a time point of
detectable disease
|
| PET/CT |
Permits detection of lesions demonstrating metabolic
activity together with morphologic information and has advantage of
detecting extramedullary disease |
-100% |
Variable |
- Intermediate availability
- Hours
- Expensive
- Detects extramedullary disease
- False-negative and false-positive results with coexisting infection
or inflammation
|
| MFC (≥ 8 color) |
| Process |
Differentiates between normal and abnormal plasma cells through detection of
cell-surface marker expression |
| Applicability |
~100% |
| Sensitivity |
10-5–10-10 |
| Important considerations |
- Widely applicable and available
- Hours
- Relatively inexpensive
- Clonal heterogeneity undetectable
- Standardized by the EuroFlow consortium
- Requires bone marrow aspirate
- Fresh sample necessary
- Does not require baseline sample
|
| ASO-PCR |
| Process |
Analysis of VDJ heavy chain regions for detection of myeloma specific Ig
rearrangements |
| Applicability |
60%–70% |
| Sensitivity |
10-5–10-10 |
| Important considerations |
- Intermediate applicability and availability
- Days to weeks
- More expensive
- Clonal heterogeneity undetectable
- Standardized (EuroMRD)
- Requires bone marrow aspirate
- Fresh sample not necessary
- Patient-specific primers necessary
- Requires baseline sample
|
| NGS |
| Process |
Use of high throughput sequencing to detect clonal Ig VDJ gene
rearrangements |
| Applicability |
~90% |
| Sensitivity |
10-6 |
| Important considerations |
- Limited availability
- One week or more
- Expensive, but costs decreasing
- Limited clonal heterogeneity detected
- Not yet standardized
- Bone marrow aspirate or peripheral blood sample acceptable
- Fresh sample not necessary
- Requires baseline sample or stored sample from a time point of
detectable disease
|
| PET/CT |
| Process |
Permits detection of lesions demonstrating metabolic activity together with
morphologic information and has advantage of detecting extramedullary
disease |
| Applicability |
~100% |
| Sensitivity |
Variable |
| Important considerations |
- Intermediate availability
- Hours
- Expensive
- Detects extramedullary disease
- False-negative and false-positive results with coexisting infection
or inflammation
|
Future applications and clinical potential
of MRD
A publication from the U.S. Food & Drug Administration (FDA)
discussing regulatory perspectives on MRD testing in multiple myeloma concluded that
MRD assessment in multiple myeloma has the potential to become a surrogate clinical
endpoint that could be used to support regulatory purposes for drug review.
Standardization of MRD testing and consensus within the multiple myeloma community
as to the role of MRD will be integral steps toward this end.73