Mark R. Litzow, MD: Jae, I’m going to ask you a loaded question: given the complexity of what we talked about, where do you factor transplant into approaching patients with ALL [acute lymphoblastic leukemia]?

Jae Park, MD: That’s challenging. I think we discussed that there are some presenting characteristics that make us a little bit worried, hypodiploid or some chromosome or molecular abnormalities, including Ph [Philadelphia chromosome]-like for some of these cases as we’re learning more about them. If they present early on, if we get that information two weeks into therapy or early on in therapy, these are the patients who we’ll be thinking about or at least planning for transplant, looking for some donor options. I think what’s clear is the patients who are MRD [minimal residual disease] positive at the end of the 3 months of induction 1 and 2, or after a couple of cycles of induction or the early consolidation, consolidation 1. I think if you’re MRD positive at that time, regardless of your presenting characteristics, that’s one of the worse prognostic factors that would determine the continuation of the same therapy. You wouldn’t be able to achieve a good MRD negativity or cure. These are the patients for whom we are thinking about transplant.

For those patients usually the transplant trigger happens, and we will usually give some MRD-directed therapy, such as blinatumomab in an approved setting, and then the hope is trying to get MRD negativity before going to transplant. I think we try our best, all of us, trying to get MRD negativity if possible. When it’s time to treat someone, we have our tools to do so.

For those patients who are MRD negative at induction or consolidation, or certainly the early induction therapies, I think for those patients we are continuing therapy, not thinking about the transplant unless there is an MRD rising, which speaks to—and I know we’re going to talk a little bit about—the MRD monitoring. It’s not just one and all. You have to continue to follow these markers to see whether there are small clones arising. I think for those patient populations, we will consider transplant as well.

Mark R. Litzow, MD: Ryan, Rachel, anything?

Ryan D. Cassaday, MD: I agree with Jae, particularly patients who achieve early MRD negativity, on deferring transplant. And I think one thing that I’ve come to appreciate is when we refer a patient for transplant, generally we are not only hoping that intervention is going to be effective for them, not really knowing for sure that it’s going to be effective. Unfortunately, we don’t really have good tools to know for sure who’s going to derive benefit from a graft-versus-leukemia effect.

But the other thing involves stopping a treatment that you’ve just demonstrated was very effective for that patient, meaning chemotherapy. We don’t typically continue the chemotherapy after transplant. So in a patient who doesn’t necessarily have any particularly high risk features, you’ve started chemotherapy and it has proven to be highly effective by achieving MRD negativity early, if you’re able to keep that patient on treatment, I think that is usually a better strategy than referring for a transplant. Again, with a few exceptions, some of which we’ve already noted.

Jae Park, MD: I know we are talking a lot about the frontline therapy, but if they are patients in relapse, I think that it’s clear that we definitely are thinking about transplant after salvage regimens. Hopefully they can get to MRD negativity and then receive transplant. I think that is a clearer setting.

Mark R. Litzow, MD: Agreed.

Rachel E. Rau, MD: On the pediatric side, we conduct transplants on far fewer of our patients with B-cell or T-cell ALL, particularly in the upfront setting. I think the one population of patients that has emerged recently that probably warrants consideration of stem cell transplant at first CR [complete remission] are those who continue to be MRD positive at the end of our second block of chemotherapy, called consolidation. And that seems to be really only amongst the NCI [National Cancer Institute] high-risk patients. And so that’s a group of patients where, since that finding, their event-free survival was around 40% without transplant. People have been referring for transplant.

We are now in the Children’s Oncology Group studying if CAR T [chimeric antigen receptor T-cell therapy] can be a definitively curative therapy for that group of patients on AALL1721. So that’s an exciting trial where we can say, can we save them from bone marrow transplant by using CAR T instead?

I think as far as patients in relapse, we actually don’t do transplants on all of them. We know there is a subset of patients who can probably be cured even after relapsing with chemotherapy alone. And those are patients who have isolated bone marrow and had bone marrow relapse that occurs later, 36 months or more, after diagnosis. And some of the isolated extramedullary relapsed patients, if they relapse more than 18-months post initial diagnosis, those patients can be salvaged to chemotherapy alone as long as they respond to their reinduction regimen to an MRD of less than 0.1%.

Transcript Edited for Clarity