Multiple Myeloma
Myeloma risk stratification rests substantially on cytogenetics. High-risk lesions identify disease that behaves differently, and their presence or absence shapes the whole discussion.
Disease categories
Major disease categories
- Multiple myeloma
- Smouldering myeloma
- MGUS
- Plasma cell leukaemia
- Amyloidosis
Molecular
Molecular considerations
del(17p), t(4;14), t(14;16) and gain(1q) are among the lesions used in risk stratification. TP53 alteration carries adverse weight.
Markers commonly discussed in multiple myeloma
- del(17p)
- t(4;14)
- t(14;16)
- gain(1q)
- TP53
- Serum free light chains
- M-protein
- MRD
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Fluorescence in situ hybridisation on CD138-selected plasma cells is central; broader sequencing is used in research and selected practice.
Germline
Germline considerations
Considered where family history is suggestive.
Molecular monitoring
ctDNA and liquid biopsy considerations
Measurable residual disease in marrow is the established monitoring approach; circulating assessment is an area of research.
Single-cell & computation
Single-cell and algorithmic approaches
Haematological malignancy is where single-cell analysis is most directly applicable, because the tissue is already a cell suspension. Single-cell DNA sequencing resolves whether co-occurring alterations sit in the same clone or in competing clones — a distinction bulk sequencing cannot make and which changes the interpretation substantially. Single-cell RNA analysis characterises differentiation state and microenvironmental interaction. Algorithm work includes measurable residual disease detection at high sensitivity, clonal phylogeny reconstruction across timepoints, and risk models built on combined cytogenetic and molecular features.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has cytogenetic risk stratification been performed on selected plasma cells?
- Is measurable residual disease being assessed, and by what method?
Resistance
Resistance and recurrence questions
- Has cytogenetics been repeated at relapse, given that the profile can evolve?
Trials
Clinical trial considerations
Risk group and prior therapy classes shape eligibility.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.