MRD Testing in Hematologic Malignancies

Panelists: John Leonard, MD, New York-Presbyterian/Weill Cornell Center for Lymphoma and Myeloma; C. Ola Landgren, MD, Memorial Sloan Kettering Cancer Center; Alexander Perl, MD, Perelman School of Medicine, University of Pennsylvania; Anas Younes, MD, Memorial Sloan Kettering Cancer Center


John Leonard, MD: That has been a great overview, and I think that we want to make sure that we allow time for questions. I think it’s funny because we got a number of questions in advance from people and that you all, in your discussions, have really hit them. So, I think it really shows that the audience is on the mark about what people are thinking about and asking about. At the very end, before we wrap up, I’m going to ask each of you to give me your thoughts on what exciting things are coming forward that we haven’t talked about in each of your areas. But first, we had a question on MRD testing, and I think I’m going to ask each of you, actually. I’ll start with Anas so everyone can catch their breath. In each of the respective areas we’ve talked about, where is MRD testing going? First, in lymphoma?

Anas Younes, MD: I think for lymphoma, there are 2 questions that need to be answered. The first is, can liquid biopsies or MRD testing, whatever you want to call it, predict clinical relapses so you can see the patient and the multiple imaging studies throughout their lifespan, especially the chronic diseases where you have multiple relapses in a lifetime like follicular lymphomas, and also in mantle cell lymphomas? The second question, especially if you’re shooting for a cure and improving the outcome, if you detect MRD or circulating tumor DNA, is it actionable? And if it is, how do you design treatment based on that?

Alexander Perl, MD: I think for leukemias, we have a long history of using MRD to drive our therapy. In CML, we’ve been doing that for years, looking at these variable levels. In ALL, we have a lot of experience with flow-based MRD, and that’s actually taking over as the primary way we’re gauging response, particularly in younger patients, and making therapeutic decisions based upon that. It’s much harder to do this in AML. To do flow-based MRD for AML is technically very challenging. There’s a limited number of places that really feel confident enough to give you a report at all, and intracenter variability is quite significant. So, a lot in the field are moving towards, can we use a mutation-based assay? And then the question is, what do you go to after?

There’s actually an interesting late-breaking abstract on this topic looking at following next-generation sequencing on multiple time points to see, do you clear mutations, and do you clear all the mutations or some mutations? And that actually may emerge as an important way to ask, are you getting a deep enough treatment response? We’re really not quite ready to use MRD to say we have the right answer for every patient. But for certain subsets, particularly nucleophosmin-mutated patients, the data really are there. That is a way that we can follow-up patients. And the big question that we have is, if you change therapy, does it change outcome?

John Leonard, MD: Ola?

C. Ola Landgren, MD: In myeloma, it’s already in the clinical criteria for response evaluation for clinical trials. It came out last year in the most updated revision. I think the field is moving from old flow cytometry assays into VGJ-based sequencing. It has at least 10 times higher sensitivity, much more reproducible. And the data, I mentioned some of the French data, suggest that that’s where you start seeing the plateau in terms of progression-free survival. So, I think it’s going to be very important to move into the direction of that. I do foresee that we could have drugs approved in multiple myeloma based on MRD as a surrogate endpoint because the data from 2 metaanalyses show that there is a very strong correlation of progression-free survival. More work to be done, but that’s going to happen.

Transcript Edited for Clarity 
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