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ASH 2021 | The role of MRD in the management of indolent NHL

Robin Foà, MD, Sapienza University of Rome, Rome, Italy, gives an overview of his talk on the clinical value of measurable residual disease (MRD) in indolent non-Hodgkin lymphoma (NHL), with a focus on follicular lymphoma (FL). Prof. Foà discusses the role of MRD monitoring in stratifying patients into different risk categories at diagnosis, as well as in refining the degree of clinical response to treatment and in predicting progression-free survival (PFS). In addition, the value of MRD in molecular testing and in helping treatment choice will also be examined. Despite its wide use in clinical trials and a large body of evidence demonstrating the benefits of MRD monitoring, it has not yet been implemented in clinical practice. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

Transcript (edited for clarity)

So they asked me this year to cover this, I would say probably, “interesting” topic. But it’s rather unusual that this is actually discussed. So they asked me to cover this and I decided to accept it because it’s as I said, not something that’s usually covered. But there’s been a lot of work on the role of MRD, minimal, measurable, depends how you mention residual disease in indolent and Hodgkin lymphoma...

So they asked me this year to cover this, I would say probably, “interesting” topic. But it’s rather unusual that this is actually discussed. So they asked me to cover this and I decided to accept it because it’s as I said, not something that’s usually covered. But there’s been a lot of work on the role of MRD, minimal, measurable, depends how you mention residual disease in indolent and Hodgkin lymphoma. I decide to do it, and I covered almost exclusively both in the text and a presentation, follicular lymphoma, which is obviously most frequent disorder we are talking about to the field of indolent and Hodgkin, and the one where we have the data. So I focused on that. So what can I say? First of all, that minimal residual disease can be monitored, but not in all cases.

So that is one of the first points that I think we should underline, because the genetic lesion is not present with the tools we have today in every single case. Where we have it, this can be used to monitor minimal or measurable residual disease, MRD. So I’ve covered more or less of, well, different aspects on how MRD monitoring can be of value clinically. But that’s what we want to know really. So I cover different topics, how this can be valuable, the amount of MRD you can detect at diagnosis in blood and marrow, and how that can impact the response to treatment. So it been mainly MRD treatment and outcome. Now, not to make a too long, but just to summarize a few points, I think it’s worth saying that in general, there’s evidence in different settings that this is exactly the case that we in fact see that this can be of value in different situations.

So while I did, because actually that’s how ASH wanted to organize a session. I started with two clinical cases because they wanted to do it rather interact in a way. So they asked us to present the few cases. I prepared a couple of cases, which I thought were relevant to a topic I was planning to cover these real cases, obviously. And based on that to be a bit more precise, I try to cover five different MRD related topics. So one I mentioned is tumor burden. A diagnosis is that useful to stratify patients in different risk categories? Then I cover, can MRD refine the degree of clinical response to treatment? Is that in a way? And the third point I covered, can MRD predict progression-free survival? So it’s a third clinical point of potential MRD monitoring.

And this is another point, if we do different molecular testing over time, is this of clinical relevance rather doing only one test, if we do more? And the other, which is obviously one of the key points in general, in the field of minimal residual disease is, can we use MRD to personalize, to modulate treatment? So could that be an indicator of different treatment? So I won’t go in detail of all of these, because that’s obviously quite extensive, but the bottom line is, and in general, I think it’s fair to say that MRD, based on data that we published. And it’s interesting here that the first data go back, let’s say, I would say more than 20 years. So it’s not a last minute aspect that we’ve been investigating. In fact I remember we started when I was still in Turin, north of Italy. And I think our first paper was if I remember well published, in fact, in blood in 2002.

So it was published 2002, you can imagine the study had started years earlier, so goes back 25 years or so. An interesting point, despite the fact that we started working on this aspect about quarter a century ago today, MRD is still not used routinely in a clinical practice, not an agreed prognostic market that should be used. I think it’s important to say it’s not in the guidelines on, let’s say the recommendations although the data are quite compelling in different areas I mentioned. Then to go towards the end, I tried to discuss how things are going to change. Because as I mentioned the beginning in not in all cases, we have a marker that we can monitor molecularly for MRD.

So now we are trying with more sophisticated technology to see if we can utilize the technology to have a marker for a broader proportion of follicular lymphoma patients. Then the other, one aspect I also mentioned at the end is again, the technologies are evolving and another one which is becoming rather widely used, although again, not still in indication in general is that of the so-called plasma DNA, so monitoring circulating markers in the plasma of patients. So we are not talking of testing a marrow or blood, but on the plasma. Which in lymphomas in general is of interest more I would say, in aggressive lymphomas and in indolent lymphomas, because the plasma, the circulating DNA could offer a better picture of the genetic landscape of individual patients.

Because if you study for instance from a genetic point of view, the lymph node, that you’re biopsying that one lymph node, but the lymphoma seen in general, not specifically here, or indolent. But the lymphoma obviously can impact or involve different lymph nodes. And if you do as we all do a biopsy in one lymph node that may not mimic the whole scenario of the genetic landscape of that given patient. Now, if the genetic MRI can go from the lymph nodes, plural, in general into the bloodstream.

So in theory, you can have more data in plasma DNA. And this has been shown in aggressive lymphomas, not in indolent. But I’ve just brought this up to say how technologies are evolving over the years. And as I said, just to finish, I think I conclude that it’s not in routine clinical practice MRD monitoring in indolent lymphoma, follicular lymphoma, saying, although there are many studies in fact that are using that to modify treatment. We’ve done it in localized indolent lymphoma, and we are modulating treatment according to the presence or absent of MRD in the patients who can be monitored. So this in clinical trial is certainly something widely done. It’s not in a day to day clinical practice yet.

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