Under the lens: Laboratory techniques for the diagnosis of multiple myeloma

Dr Bruno Paiva - Clinica Universidad de Navarra, Pamplona, Spain

Yesterday we briefly reviewed what are the techniques that are available and should be performed in the laboratory for diagnosis and monitoring of patients with multiple myeloma. These techniques involve methods that measure proteins and methods that measure cells. We also briefly mentioned about techniques that perhaps are not the gold standard but could be an interesting option in the future. For example, whereas for measuring the M protein, we still rely on electrophoresis and immunofixation, eventually in the future mass spectrometry could be an interesting option.

Then, from a cellular point of view, we review what are the cytogenetic alterations that are associated with high-risk myeloma, that these are currently methods measured by FISH on CD138 isolated plasma cells. But we also talked about the option that in the future it could be possible to have information on copy number alterations, translocations and mutations in a single test using next generation sequencing. While this is being currently investigated and performed in clinical trials in tumour cells and bone marrow aspirates, it is also possible that in the future this kind of information can be obtained in the blood or in the plasma based on circulating free or circulating tumour DNA, so genetic screening using minimal invasive procedures.

Then from a cytology point of view we reviewed that morphology is still highly useful to make differential diagnoses between MGUS and myeloma, also based on 60% of plasma cells in the marrow that this is a myeloma-defining event. Then you also have flow cytometry as perhaps a more sophisticated cytologic approach to measure, for example, with high sensitivity to the presence of circulating tumour cells in peripheral blood. This is of clear prognostic value, also to identify patients with myeloma and a more immature phenotype which is associated with poor prognosis and, last but not least, characterisation of the immune microenvironment which can become more and more relevant with the progressive usage of immunotherapies.

This is a diagnosis, then, to monitor treatment efficacy, and we believe that if it is so important to stage and characterise the patient at diagnosis, it is equally important to define the quality of response with exquisite sensibility and sensitivity. This means using next generation methods to monitor MRD on top of conventional CR. For this, there are next generation sequencing, next generation flow, they are providing the same reproducible results and these are outstanding. We are seeing that nowadays an undetectable MRD is associated with approximately an 80% reduction in the risk of progression after treatment. We also realised that both technologies have some limitations, I think the most important one is the fact that they don’t measure potential extramedullary disease and therefore it is important to know and understand if not all patients at least those patients in which it could be mandatory to combine either next generation sequencing or next generation flow with PET CT for well-defined undetectable MRD results.