Other prognostic factors: minimal residual disease

Despite the fact that myeloma patients may achieve CR or sCR with treatment, the vast majority will retain some level of remaining (residual) disease that is undetectable either by serum and urine protein electrophoresis, immunofixation, serum FLC assay or bone marrow immunohistochemistry. This is known as minimal residual disease (MRD) and is the cause of an eventual relapse.

Importantly, the presence or absence of MRD using sensitive methods is also recognised to be a strong prognostic indicator. Patients achieving undetectable MRD (MRD negativity) are more likely to have better outcomes.

However, unlike other haematological malignancies such as acute lymphoblastic leukaemia, measuring and monitoring MRD has yet to become a standard of care in myeloma. This is due to a lack of consensus about which technique is most sensitive and what needs to be accomplished to further optimise response criteria. MRD is used as a marker of response and/or primary end point in clinical trials.

Techniques currently used include:

• Multiparametric or next-generation flow cytometry
• Whole-body MRI and or PET imaging
• High-throughput next generation sequencing
• Mass spectrometry

Patients who have no signs of residual disease are described as being MRD-negative, while those with signs of residual disease are classed as MRD-positive. Evidence indicates that MRD-positive patients relapse more quickly. Therefore, MRD status may be useful in predicting survival outcomes to treatment and the depth of remission.

The clinical benefits of MRD monitoring continue to be investigated in different clinical trials and hopefully will provide the rationale for its use as part of standard clinical practice in the near future. Coupled with other well-established markers, MRD assessment holds promise for improving the stratification of patients into specific treatment pathways. Considerations of how to counsel patients on their MRD status as a measure of disease response need to be taken into account.

Further reading

Szalat et al. (2024) Role of minimal residual disease assessment in multiple myeloma. Haematologica. doi.org/10.3324/haematol.2023.284662

Ding et al. (2021) Minimal residual disease in multiple myeloma: current status. Biomarker Research vol 9, Article number: 75

Kostopoulos et al. (2020) Minimal Residual Disease in Multiple Myeloma: Current Landscape and Future Applications With Immunotherapeutic Approaches. doi: 10.3389/fonc.2020.00860

Pavia B et al. (2015) New criteria for response assessment: role of minimal residual disease in multiple myeloma. Blood 125(20): 3059-3068.

Kumar S et al. (2016) International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 17(8): e328-346.