EBMT 2021 | Response monitoring in multiple myeloma

This was an educational activity targeting the data managers and statisticians. And I was asked to give a review on myeloma response and as in all other diseases, response is the hallmark of success. For this reason, it’s very important, and for plasma cell dyscrasias, it’s rather complex and it’s a continuously evolving topic as well because we are getting to know the disease better. And also, the newer tools are being introduced to measure disease activity and also disease burden.

With this aspect, the IMWG has published new guidelines, and during this educational activity I gave a historical background of the diagnosis of myeloma and the parameters which are required, because I’ve been involved in EBMT activities for a very long time, and there’s a big problem rising from the lack of data such as diagnostic parameters, which are really important for prognostic evaluation. For this reason, I wanted to give an emphasize on the importance of these initial parameters because these are also important for response assessment and also prognosis evaluation.

For biochemical response, the newer tools such as urine and serum free light chain measurements has become more standardized and there is currently not much need for urine measurement, as a serum free light chain assessments replaces for this need. This was one of the important issues because it also enabled us for stringent CR determination.

And furthermore, we have additional tools which has been verbalized during the EBMT multiple times, and that is minimal residual disease assessment. During the last 10 years, there has been progress in the field of multicolor flow cytometry, which is now taking in the place for next generation sequencing. Maybe it will enable replacement of a flow cytometry assessment. And the importance of sensitivity, which was initially 10 over -4, and has now gone up to -6, which gives a better measurement of residual disease. And this is another issue, what time and how frequent they should be done? And we now know, and during the EBMT it has been repeated multiple times, that for post-induction MRD assessment is important.

So, during the EBMT 202, the importance of MRD has been announced multiple times, and what is new is the timing of MRD has been discussed in some of the sessions with post-induction MRD being of importance. And also, sustainability of MRD is another issue, repeated, repeating MRD every six or at least every year, and the duration of a sustainable and continuous MRDs is a new parameter that may be a reflection of a cure coming in the future.

And the other tool for disease assessment is PET-CT, and PET-CT gives the advantage of global disease measurement. The Deauville criteria has been now introduced to multiple myeloma, and it will be combined for many studies in future. Regarding the positioning of MRD in the new trials, we have heard during the EBMT that the new IFM study will randomize patients based on their MRD negative to continue therapy versus stopping therapy.

A similar approach is valid for the EQUATE study from United States, where they will be adding a new agent in terms of the response based on MRD assessment. So, certainly, response assessment will be, will stay, remain an important part of our treatment strategies, and cure, in terms of functional cure in another terminology, is going to be repeated more because of the new quadruplets prior to transplant is going to achieve MRD negativity very early, and [inaudible] transplant will be a consultation, unlike the earlier times where it was not so successful.