IMS 2026 | Whole genome sequencing of circulating tumor cells in multiple myeloma

Yes, we know that the genetic abnormalities in myeloma play an important role in prognostication and to an increasing extent has started allowing a better selection of therapy for patients. Now the downside of the genomic testing that we currently do is that it needs bone marrow which is an invasive procedure and cannot be done very frequently. We know the bone marrow is important for a variety of reasons, important also for determining if a patient is MRD negative, an important metric with the current therapies that we use in multiple myeloma. The genomic sequencing has become even more important with the recent IMS-IMWG consensus genomic score that requires sequencing to allow assessment of any mutations involving the TP53 gene. So there is increasing interest in doing genetic sequencing in multiple myeloma. There is also emerging data that mutations involving the BCMA as well as other targets for immunotherapy can have implications on whether these therapies work well or how long they work for in a given patient. And with the increasing numbers of choices of therapy we have in the immunotherapy space, there is a unique opportunity for us to decide on a therapy based on the abnormalities that we might find with respect to the target for each of these therapies. Again, the challenge there is we cannot keep repeating the bone marrow biopsies to do these genetic studies. So there have been multiple studies looking at exploring circulating tumor cells or circulating tumor DNA to do some of these studies. We know that in patients with myeloma, particularly relapsed disease, nearly 100% of these patients can have circulating tumor cells. There’s increasing sensitivity of the assays that we use, which allows us to focus on these small numbers of cells in the circulation to study the genomic abnormalities in those cells. Now, even in the absence of these cells, we know we can identify circulating tumor DNA or cell-free DNA originating from the tumor cells in the peripheral blood in the vast majority of the patients. So both these sources allow us to interrogate the tumor cells or the tumor material for mutations that we typically see in myeloma. So the use of peripheral blood to interrogate and identify these genomic abnormalities we just talked about, whether it be prognostic abnormalities like the TP53 mutation or there are particularly relevant abnormalities like mutations in the BCMA receptor, all of these would be of great value. And we think the technology has continued to evolve that we can actually do these things in the peripheral blood with a lot more sensitivity and specificity than we used to in the past. Now, how they compare with the bone marrow is still a work in progress. We know we can identify most of the abnormalities, but what we don’t know for sure is whether we can do that in a hundred percent of the individuals or are there other characteristics of the disease like the proliferation rate and specific secondary abnormalities that might make these cells more likely to circulate in a given patient so there are still some details that need to be worked out overall, it seems like we are getting closer and closer to being able to get most of the information we need from the peripheral blood. This will allow us to not only avoid invasive procedures, but also be able to monitor this frequently over time so that we can monitor the changes for the duration of therapy. And of course, there’s increasing focus on using peripheral blood-based testing for MRD assessment in patients with myeloma as well. Again, trying to avoid the bone marrow except when absolutely needed. Yeah, I think it might take a little bit more time for us to be able to broadly implement these assays as there are several details that need to be, you know, figured out. Obviously, it needs some kind of regulatory authority approval for us to be implementing this in the clinic. And then we also need to have a better understanding about how to use them and how to interpret the results that we get out of those. I think once those things are clarified from existing data as well as prospective studies, I think it’s going to be prime time for its use broadly in the clinic. And I anticipate in the next two to five years timeline for that to happen.

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