Technological advances in MRD assessment
Dr Bruno Paiva - Clinica Universidad de Navarra, Pamplona, Spain
It’s all about data integration and finding synergism and complementarity. In fact, the most interesting evidence we are seeing in emerging data from the new clinical trials with modern, highly effective therapy as well as next-generation tools to characterise the patient, is the fact that in myeloma risk is dynamic. What I mean is that the patient can be or can have high-risk disease at diagnosis, but if the patient achieves a deep response to treatment, and I’m alluding to a negative MRD result, with a limit of detection of 10-6, this patient gets upstaged to standard risk myeloma because progression-free survival is identical to those patients with standard risk myeloma also achieving a negative MRD result.
By contrast, if a patient starts with not high risk, standard risk disease, if there is persistent disease almost implies that the patient has turned into a higher risk feature. Therefore the concept that risk is dynamic in that we can appreciate challenges or changes in patients’ risk if we combine initial upfront risk stratification together with sensitive assessment of response to treatment.
How have these advancements improved the assessments we use today?
It’s outstanding, because in only a few years we have seen great improvement and advances in the way we monitor MRD, both from a cellular point of view, we have the low sensitivity flow cytometry in the past together with equally important many different protocols being done in many different laboratories, therefore lack of standardisation. On the other hand we have ASO PCR as a molecular approach, and perhaps this was more standardised but was also time and labour consuming and was not applicable to a significant fraction of patients. Nowadays we have next generation flow that is fully validated, optimised and standardised by the EuroFlow Consortium, is being used in many different hospitals around the world and has the same sensitivity as the molecular methods. On the molecular methods we have now next generation sequencing that perhaps is slightly more sensitive than ASO PCR but most importantly applicable to more than 90% of myeloma patients.
On the other hand we have PET CT that is becoming more and more used that is providing very important results, and even on PET CT we are seeing some innovation regarding, for example, the tracer that is being used to detect uptake in those myeloma cells.