Krishna V. Komanduri, MD: A couple of practical things since we do have an FDA approval: Obviously, the Novartis approval of tisagenlecleucel came first. I think from Michael’s and David’s perspectives, I’d love to hear what you think. And I know you understand the label. Which patients right now should be referred here in the pediatric population and the young adult population, given where the label indication is, for therapy or for consultation?

Michael Pulsipher, MD: So, the label very specifically says refractory or multiply relapsed ALL. That’s exactly what we want to see. If patients do not go under remission with initial induction therapy, we need to see them. If patients relapse, especially if they relapse multiple times, they very much should receive this therapy. If patients relapse after transplant, it’s really one of the only salvage therapies. Second transplant works in very rare cases, but treating these patients with tisagenlecleucel after relapse after transplant can cure most of them. And so, I think those are right on target. For the future, we’re trying to go even earlier and identify very high-risk patients. But for now, and for the current label, I think those are the patients we’re looking for.

Krishna V. Komanduri, MD: David, would you add anything for the young adult patients, or do you agree with that?

David Maloney, MD, PhD: I certainly agree with that. Obviously, people want to try to move this up into the high-risk population, even potentially earlier. I think there’s no other treatment that has shown this degree of activity ever in the treatment of relapsed/refractory disease. There are other treatments out there: blinatumomab, inotuzumab, ozogamicin. But even if you look at those progression-free survival curves, most patients relapse within a year. And so, I think this should be moved up in the scheme of things and we need to get it, as we were talking about earlier, into the adult population.

Stephen J. Schuster, MD: Yes. Certainly, the standard therapies are much less successful in adults than in children. So, I think there’s a much larger unmet need among adult patients with ALL.

Krishna V. Komanduri, MD: One, again, practical thing—since many of the individuals who are trying to get this information may not know this—roughly how many sites at commercial launch for Novartis or for KTE will be doing the therapy, at least in the very short term?

David Maloney, MD, PhD: Well, I think that both companies are quite wise in their rolling this out slowly into centers that have expertise. I think that’s critically important. Of course, I’m at one of those centers so maybe I’m speaking wrongly here. But I think we really need to have experience with managing cytokine release syndrome and neurotoxicity, at least initially. As we develop the algorithms on how to prevent or even preempt some of these toxicities, then I think it could be ruled out. So, right now, it’s just a matter of getting and referring patients early enough to those sites to be able to be treated. Obviously, having capacity. Right now, I think both companies seem to have capacity but we’re really early in the game.

Krishna V. Komanduri, MD: We’re really at launch; we’re talking about less than a couple of dozen sites for each of the sites.

Michael Pulsipher, MD: On the pediatric side, one of the ways that we facilitated doing this was to involve a large number of very experienced centers with the approval trial. So, we had 15 United States centers, a total of 25 international centers. Now in the United States for the commercial product, 33 to 35 centers have been designated. Twenty-three of them are active right now and are working very hard to try to cover areas of the country so that people, when they refer, don’t have to refer in extreme distances. But yes, these centers need to gain expertise. Over time more and more centers will be doing this, but it takes time, effort, and resources to figure out how to do this.

Krishna V. Komanduri, MD: And I would point out that things are going to be very similar for KTE and, having again been part of some of these early studies, we know how difficult they are, we know the kinds of toxicities that we discussed earlier and how, at least initially, we all believe that this is something that should be done in highly specialized centers. And as we develop experience and we disseminate that information academically, we learn more. Obviously, the range of centers that will do this will broaden quickly.

David Maloney, MD, PhD: Yes. And I think it’s also just important to remember that in pediatric and young adult ALL, this is a small problem. It’s a big problem for the patients who have relapsed/refractory ALL, but the number of patients per year is estimated at maybe 600, so it’s very small. Contrast that with replaced B-cell lymphoma where 50% of people relapse, and we’re talking 10,000 or 20,000 patients.

Stephen J. Schuster, MD: That will stress the system. That will test the capacity.

Michael Pulsipher, MD: We were talking about this in a meeting yesterday where this is going to be going to 100 centers rather than 30 centers, and how difficult that is going to be to scale up. We’ll see this happening over the next few years, but it’s going to be a big challenge.

David Maloney, MD, PhD: Agreed.

Transcript Edited for Clarity