ASH 2024 | A study investigating MRD conversion in patients with multiple myeloma on lenalidomide maintenance

So, I’m quite excited about this particular study. This is a study that really informs what to do with MRD conversion, or at least begins to inform on that. I think one of the most interesting aspects of what the myeloma community has learned over the past number of years is the implications of sustained MRD negativity, as well as the implications of sustained MRD negativity, which implies a very good outcome and in some cases, as presented at this meeting, allows us to stop treatment. So, however, what do you do in individuals that have MRD negativity, but then they have a return to MRD positivity? So that is, do you automatically change treatment or not? So there is some data presented by others here from the MASTER study that suggests that early MRD resurgence or MRD resurgence after quadruplet therapy with daratumumab, IMiD, PI, and dex is a harbinger of very poor outcomes and necessitates treatment change to an alternative treatment modality. However, when you have late MRD resurgence, it’s not entirely clear what to do. So this abstract draws on our natural history study, evaluating 108 patients that were receiving lenalidomide and were being monitored on an annual basis for MRD status. Among these individuals, at study entry, approximately half were MRD positive and half were MRD negative. And then a cohort of patients, fortunately a small group of patients, converted to MRD positivity. But what was striking when we follow these patients over time is that conversion to MRD positivity did not automatically mean that individuals progressed. Over half the patients that converted to MRD positivity had not progressed for two or more years. And so we evaluated the peripheral blood available on these patients that was collected quarterly for T-cell immune phenotype. And what we observed is that an activated T-cell phenotype is present among individuals that convert to MRD positivity from MRD negativity and then go on to progress, whereas a less activated T cell phenotype or one that’s sort of inactive or more normal-like is associated with ongoing durable remission. And what’s sort of striking here is that half of our cohort was MRD positive at the entry point and a proportion of those patients also were durable non-progressors. And so if we then look at the T cell immune phenotype of the individuals that are MRD positive, the ones that do not progress are most similar to the folks that convert to MRD positivity and don’t progress, suggesting that the immune sort of MRD phenotype or like a separate immune reflection of progression versus not distinct from MRD status, which we can call immune MRD, and which I think suggests a panel of testing that can be evaluated in our patients to help inform natural history of disease in a complementary way to MRD status focused on the plasma cells.

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