Mark R. Litzow, MD: Well, let’s get our crystal balls out and talk a little bit about what we see in the future. Jae, could you talk about where you see MRD [minimal residual disease] testing going, and how we may continue to refine that?

Jae Park, MD: You stated earlier that MRD was this newer term, measurable residual disease, and I think the level of the sensitivity of detection is getting better. We were talking about 10^-4 and then obviously we have the tools to get much deeper than that, 10^-6, and I think it will probably go even deeper soon. So the question will remain, with the better tools that we’re definitely going to have, how is it going to impact our treatment at that time? I’d say we’re going to get a lot more data. But then the COG [Children’s Oncology Group] is already exploring this for those patients who are 10^-4 MRD negative, but NGS [next-generation sequencing] detectable or below; should we change the dose management for those patients or not?

I think the technology will get better; we’ll be able to pick up the smaller levels of a disease. The more challenging thing is what to do with that information. For that small disease, is it worthwhile to intensify or change the therapy that has been previously working or just continue with it? Hopefully we can address these issues in large trials to really answer them, rather than borrowing the data piecemeal. Hopefully we can do that.

Ryan D. Cassaday, MD: I think one of the things that is a drawback of these DNA-based MRD detection methods, particularly in the future as we start to bring more of these targeted immunotherapeutic agents earlier in the lines of therapy, those methods don’t tell us about CD19, CD22 expression. It’s not really so much of an issue if they haven’t received one of those agents. But, in the future, if we start using blinatumomab or CAR [chimeric antigen receptor] T-cell therapy or inotuzumab ozogamicin in the frontline setting, we know that those agents can downregulate expression of the targeted agents. So if we are detecting at these super low levels, but we don’t know anything about the immunophenotypic features, we may give them blinatumomab, but there’s no CD19 there to target. So I think that’s going to be one thing that, as a field, we’re going to have to be cognizant of and sensitive to as not only the methods get better, but these targeted agents get moved into therapy sooner.

Mark R. Litzow, MD: There’s something there, but we can’t tell what’s on the cell.

Ryan D. Cassaday, MD: Exactly right, exactly right.

Jae Park, MD: I think that’s actually a very important point, because now we have blinatumomab, and as you were alluding earlier, there are two options for CAR T-cell therapy. If they receive blinatumomab, are we going to be selecting resistance, which the majority of the patients don’t experience, but there could be some settings where that occurs. But you have to look at the plot sometimes, and we have to talk to these hematopathologists to really let them review the plot and ask if they see any CD19-negative clone, because you’re worried and it may change your management. So as these CD19-targeted therapies are used earlier and earlier, I think it’s important to really let the hematopathologist know that these patients have received CD19 targeted therapy. Therefore, you need to add additional B-cell antigens to make sure that we target successfully, especially for flow cytometry based assays. NGS obviously may not matter as much, but I think that’s an important point.

For the future MRD, I think hopefully, we talked a lot about the bone marrow-based testing. As the sensitivity is getting better, what I’m actually hoping is that we can move away from doing bone tests multiple times and some blood-based testing could be just as sensitive. I think that’s where this more sensitive testing can hopefully help our patients to lessen the amount of the procedures that they have to go through.

Mark R. Litzow, MD: Yes, exactly.

Rachel E. Rau, MD: I think the data would suggest that it’s about a 10-fold difference, bone marrow to peripheral blood, and if you can achieve 10^-6 in the bone marrow at that time point, then that would translate into 10^-5, which is more than sufficient.

Ryan D. Cassaday, MD: A reasonable amount.

Rachel E. Rau, MD: I think it’s exciting and generating more data to that regard might save some patients from some painful procedures, which would be great.

Transcript Edited for Clarity