ASH 2025 | Novel insights into the value of CTCs in myeloma and smoldering myeloma

In connection with what we have talked about the smoldering patients, we have analyzed now in over 300 smoldering patients the presence of circulating tumor cells. And we have found that 73% of the smoldering patients have circulating tumor cells, and according to the level of circulating tumor cells, you can predict the risk of progression. In fact, we have established a threshold that is 0.02% as a risk of progression for 50% risk of progression at two years. And it’s interesting just to realize that you can replace the 2/20/20 classification instead of using the 20% plus plasma cells, you can use 2%, 0.2% circulating tumor cells and the prediction is a bit better and on top of this this is this can be a dynamic parameter because you can reevaluate every three months every four months what is the proportion of circulating tumor cells and if you see that there is an increase, it will be similar to the increase in the M-component, the evolving pattern, or the decrease in the hemoglobin. And in fact, we have seen that this evolving pattern of decreasing hemoglobin and increase in the number of circulating plasma cells, can predict very precisely the risk of progression in a smoldering patient. 

On top of this, talking about circulating tumor cells, we have analyzed in over 3,000 myeloma patients, a subgroup of cases, this now I’m focusing on active myeloma, there is a group of patients that represent approximately 10% of the patients that do not have circulating tumor cells. The vast majority of active myeloma patients have circulating tumor cells, but there is 10% of the patients that do not have circulating tumor cells. And these patients have an outstanding outcome and probably don’t need a very intensive treatment because they are more like an MGUS profile, like a smoldering profile. And in this patient, in addition to the large PFS, the incidence of anemia is less, the incidence of revised ISS3 is less frequent, tumor burden is lower, and interestingly, the presence of plasmacytoma, soft tissue plasmacytoma, is more frequent, probably reflecting that this is distinct biology from the rest of myeloma patients. 

And last but not least, talking about circulating tumor cells, I think we should, another oral presentation, one of five oral presentations from a group on this topic, was the value of circulating tumor cells by blood flow to assess minimal residual disease. And we have found that circulating tumor cells by blood flow can be very useful, particularly during the maintenance therapy. In order to avoid the frequent requirement of bone marrow exams for evaluation of minimal residual disease in the bone marrow, this minimal residual disease in the bone marrow is mandatory in the early phase of the treatment, during the induction, immediately after transplant, consolidation. But during maintenance, probably you can do the bone marrow exam once every six months, once a year, and in the middle, every three months, you can do the circulating tumor cell analysis by mass spectrometry. And this will allow you to spare the frequency of bone marrow exams and to predict early relapses by using the circulating tumor cells. Then a lot of information can come from this.

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