ASH 2022 | Using single-cell RNA-sequencing to identify biomarkers of progression in patients with SMM

So one of the questions we always ask ourselves is, who should we treat for smoldering multiple myeloma and who should we not treat? Because you don’t want to overtreat patients who should not actually be treated, and therefore you should not be exposing them to therapy. And there are people who will progress to myeloma in the next one or two years, and you want to make sure those are the people you intercept early, and make sure that you prevent end organ damage in them. And right now our clinical markers, 20/2/20, are good, but not good enough for us to stratify patients. So we said, let’s look at the genomics as well as the immune cells. And we started to look at it at the single-cell level. And that’s critical because single-cell level can really give you that complexity of all of the data, and trying to understand truly which cells are critical for progression, and can we understand what is the biology behind it. And then now we can use it to develop biomarkers for our patients.

So when a patient comes to me, instead of saying, “I’ll just look at your M-spike and light-chain.” I might be able to say, “Let me look at your genomics at the single-cell level. Let me look at your immune cells and tell you which biomarkers would be predictive for you to progress.” So we’ve done that and we’ve presented this ASH multiple of those studies. We’ve done single-cell sequencing of the tumor cells in the bone marrow, single-cell sequencing of circulating tumor cells. We think that a blood sample could be amazing for us to detect early who will progress and who will not. And counting circulating tumor cells is important, but understanding biologically which mutations, which alterations, are in those circulating tumor cells is also critical.

And then of course, we cannot ignore the other half of the coin, which is the ecosystem of the immune cells. And now we’ve shown the largest cohort to date, over 350 samples of immune cell sequencing. So over two million cells from the bone marrow and the peripheral blood showing you that we can use the immune system as a biomarker for disease progression, as a biomarker of response to therapy. So when we treated patients on a clinical trial, we can predict who will respond and who will not. And as a biomarker of response at the end of therapy, what we would call immune MRD, or post-immunotherapy normalization which means if you normalize your immune system post-therapy, you may have a longer remission and potentially prevent patients from going on on therapy with maintenance for many, many years. So many other studies need to be done, but we’re already starting to dissect those pathways and develop biomarkers for disease progression, as well as interception for our patients.