EHA 2025 | The role of MRD in risk stratification and treatment decisions for adult ALL

MRD is probably the one single most important factor in terms of the prognostic markers, and I think it is critical for anybody who is treating patients with ALL that MRD needs to be assessed and needs to be incorporated into the decision-making. So if you don’t, I think we can easily make a wrong decision or over-treat or under-treat some of the patients if you do not have MRD, that’s how important that marker is. And MRD, I think that what has changed a lot is that we used to have, at least in the U.S., kind of a couple of different methods, two different methods of either by flow cytometry, which requires a very specialized lab and standardized lab who are certified to perform MRD-level flow to get to the 10 to the minus 4. We now have a FDA-approved assay, which is by NGS, called ClonoSEQ, that you can send the subsequent samples to, and that can get to the sensitivity of a 10 to the minus 6. So, you know, therefore, technically to be called an MRD, that you need at least 10 to the minus 4, but with the NGS ClonoSEQ, that you are actually able to get an even more sensitive and deeper level of a remission assessment. So, NGS and MRD should be incorporated kind of into the front, both frontline, it is especially important, the most important setting is a frontline setting, because if you’re MRD positive at the end of the consolidation or around the three-month mark, those patients, regardless of their initial disease biology, or the genotypes, or karyotype abnormalities, if you’re MRD positive at that time point, that indicates a high-risk patient for different treatment interventions and possibly also considering a consolidative allogeneic transplant once they achieve an MRD negativity. And that we know the outcome of a transplant is also better when the patients are able to get the transplant in MRD negativity. So these are just to reemphasize the critical role of MRD. There are some critical time points, and that’s the thing that sometimes we wonder how often should we get the MRD level. In some cases, in the larger centers, they might be able to do samples every time they do a bone marrow biopsy. But the critical time point is at the end of induction at the end of consolidation before starting maintenance. I think the minimal time point that you need to assess MRD to make sure that you’re on the right track or do not need to make any treatment changes. During the maintenance part, I do think it’s also important to do it, especially some of the disease and if they have high-risk disease features, it can have an early relapse. So I do think it’s important to assess for an MRD periodically, whether it’s every three or six months with the bone marrow biopsies that you need to do that. In the relapsed setting, we talked about CAR T-cell therapy earlier, but it’s equally important because if you’re MRD positive, you also do know that these patients are incredibly high risk of relapse. Almost always they do relapse. So achieving MRD negativity is the first goal. It doesn’t guarantee that you’re going to remain in remission, but if you don’t, then I think that’s another strategy. So there it’s also important to assess for an MRD in the relapse refractory setting too. So again, make sure that if you are treating ALL doctors, then make sure they’re considered for the MRD assessment at these key times.

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