Multiomics Reveal MRD Kinetics & Early Immunotherapy Response in Myeloma | Bruno Paiva, PhD | #EHA2025

I'm Bruno Paiva from the University of Navarre in Pamplona, Spain. At EAJ 2025 we are presenting an oral abstract about MRD kinetics, both from the prognostic as well as from the biology point of view. From the prognostic point of view we have generated an issue in my view and it's the fact that nowadays MRD is being assessed much more frequently than in the past. Maybe three, four, five, if not more, assessments in a single clinical trial. And whereas in the past it was easy to classify patients either into negative or positive or resurgence or clearance based on two assessments, nowadays no one knows how to classify. And you have five or six different assessments. So we tried to answer this question by collecting data from almost 1800 patients, almost 4000 MRD assessments, both in clinical trial and real world cohorts. And the results were completely validated in two settings and we were able to segregate patients into three different subgroups. With sustained MRD negativity, all assessments were negative. Unprecedented outcomes, PFS and OS of almost 85% at six years and beyond. And then a new subgroup of patients with positive yet stable MRD levels for whom the PFS is not as good but is actually very positive and the overall survival is as good as those patients with sustained negative MRD. And then a subset of patients with positive and evolving MRD levels that present with significantly inferior PFS and OS. And we showed in multivariate analysis, again in the real world and clinical trial cohorts, that positive evolving MRD levels is the strongest risk factor to predict inferior progression free survival. From the biology point of view, we show that there is continuous genomic evolution from diagnosis to MRD to relax. In fact, the MRD clone is almost like a bridge in between diagnosis and relax with a lot of genetic alterations and transcriptional adaptation to treatment. And therefore based on those findings together with modulation of the bone marrow immune composition that we observe throughout treatment, we hypothesize that early interception of MRD when compared to immunotherapy at a time of clinical relapse could drive some clinical benefit. And we leverage on the mice models developed at our university by my colleague Martinez Clement to show that indeed treatment with an anti-BCMA CAR-T at a time of MRD as opposed to clinical relapse does improve survival in mice and therefore this concept should be investigated in our opinion in clinical trials.