COMy 2022 | The role of precursor conditions in myeloma

If you think about it, we know how to diagnose MGUS because it’s a simple blood test. Yet, what we need to know is understand who is truly at risk of developing myeloma. There are so many people with MGUS and smoldering myeloma who may never progress to myeloma, and we need to be careful not to over-treat those patients, but there are others who are truly on the way to overt myeloma, even if it is 5, 10 years from now. And we need to be careful that potentially we can treat them early and by early interception, can we truly cure the disease? And that’s truly a question. So risk stratifying patients, being more careful with who is truly going to develop the disease and being more precise about it will help us tell patients at the individual level, whether they are going to progress or not. And you can layer the clinical numbers that we have, the M Spike, the light chain, the percentage of bone marrow, to more functional studies. The circulating tumor cells, are they genomically aberrant or not? Can we understand better which alterations, genomic epigenetic alterations really lead to progression and then looking at the tumor micro-environment. And taking it at the single-cell level, we can then define better who is truly at risk biologically to progress. And we need to stop really using the taxonomy words of this is MGUS, this is smoldering. We had a really good discussion that 10% plasma cells is so arbitrary that you can do two bone marrow biopsies on the same patient. One will show 5%, one will show 15%. That same patient has suddenly changed from 1% per year progression to 10% chance of progression per year. And that’s not accurate for patients. So we need to really improve our accuracy so that we can actually tell our patients, you have this percent risk, not in general, your 20/2/20 is this or that.