What is whole genome sequencing? How has whole-genome sequencing been used to identify progressive versus stable myeloma precursor conditions as two distinct entities?

What is whole genome sequencing? How has whole genome sequencing been used to identify progressive versus stable myeloma precursor conditions as two distinct entities?

To this day, people are focusing on the amount of protein that you see in the blood or the number of cells that you can count with your eyes in the microscope. All these markers are basically indicators of the amount of the disease and all the so-called risk factors, show that if there is more of these precursor cells versus if there are fewer of these precursor cells. The risk is higher for progression.

What is happening right now is that there are a lot of investigations using modern technology with sequencing-based approaches and so forth, trying to see if genomic characterization, even in low amounts of disease, can identify individuals that will progress. And if all the individuals that have slightly higher amounts, higher volume of precursor disease, if all of them will progress or not.

There is data published over the past 12 to 18 months indicating that with very sophisticated sequencing, it's possible to identify cases that will progress within two years or so, and patients that have precursor disease that don't have these markers. With over 50 years of follow-up, there is no progression yet.

So where is the field going? So what's happening right now is that these novel insights are being expanded to be confirmed and expanded into larger cohorts. More advanced sequencing of low amounts of deceased cells reveals that there are two entities. There is the progressive and non-progressive precursor disease, as the field is moving forward, as more data is being generated. If these larger efforts will confirm and expand on these observations, this will erase the terminology of smoldering myeloma, and it will make it monoclonal and go more costly and it will make it myeloma.

The field is wrestling with these questions. So my prediction is that most likely I think smoldering myeloma will not exist in the future. I think we will have the monoclonal gammopathy and we will have the multiple myeloma. And I think this test will bring clarity to the space of who is programmed to progress and not.

So this is an area of a lot of investigation. And there is also a lot of controversy. And the future will tell when the field will go.