The current status for both circulating tumour cells, or CTCs, and circulating tumour DNA, ctDNA, is that there are great expectations in the field of multiple myeloma. There have been a number, a considerable number, of publications showing prognostic value and I think that the time is now for a greater consensus, reproducibility, greater insight also about clinical applications for these biomarkers to be potentially endorsed by the International Myeloma Working Group guidelines and also in the national myeloma societies.
What are the major challenges in detecting and quantifying CTCs and ctDNA in multiple myeloma?
The detection and quantification of CTCs has become straightforward, particularly with the broad availability and use of the next generation flow assay developed by the EuroFlow that enables the detection of these cells down to a sensitivity of 10-6, similarly to MRD. As for ctDNA, the technology is there. Probably we have still to find the adequate balance between the amount of information and the amount of DNA needed for that information. I’ll explain myself. The more DNA, the more information we want to obtain beyond the mutational status of a few genes, I’m thinking of copy number alterations, IGH locations, other mutations, [??] signatures etc., the more DNA you need. Therefore the technology may not be there for primetime use for a comprehensive genetic characterisation of the patient using ctDNA.
How might the use of CTCs and ctDNA biomarkers change the way we monitor minimal residual disease and predict relapse in multiple myeloma patients?
This is an unmet need because fortunately patients are living longer, much longer, because of those very favourable outcomes. There are expectations of treatment-free intervals or not pursuing fixed duration treatment until disease progression, meaning that there will be more and more interest in monitoring the patient for longer periods, meaning that traditional ways of monitoring, particularly the MRD level in the bone marrow, will clearly decrease the quality of life of patients. We cannot think about a scenario in which bone marrow aspirates are being collected every six or even every 12 months for a period of 5-7 years. This creates the unmet need for minimally invasive assessment and hopefully CTCs and/or ctDNA would be candidate biomarkers for those minimally invasive assessments.
What do you see as the future potential for integrating CTC and ctDNA biomarkers into routine clinical practice for multiple myeloma?
It’s really up to us to show the clinical application. The moment it becomes clear that these biomarkers have clinical application plus reproducible, easy to use, with consensus cut-offs, for example, in terms of quantification of CTCs, then it becomes very easy to translate into laboratory routine practice, particularly the CTC assessment. Perhaps not that easy for the ctDNA.
