DR FRIEDBERG: This really was the observation of trying to use brentuximab vedotin as a bridge to allogeneic transplant. And in fact, I would submit that anybody who’s interested in performing allogeneic transplants probably is using brentuximab vedotin as a bridge now, because it’s so active after autologous transplant.
But about a year ago, the City of Hope group presented these results that really, in my mind, were quite unique in the literature in that they had a 1-year progression-free survival of over 90% and with all patients alive who had received brentuximab vedotin and then went on to a reduced-intensity allogeneic transplant. And the reason why I think that was so surprising is that despite the young age of all of these patients with Hodgkin lymphoma, most experiences in the literature, as well as the individual experiences, were that these patients really do disproportionately poorly and tend to have very high treatment-related mortality, so probably in part because of the immunosuppression that’s associated with the underlying Hodgkin lymphoma. That’s at least my thought.
So this was an update of this. And despite those really impressive 1-year results, the 2-year progression-free survival had dropped from over 90% to 57%. And there were deaths that had already occurred. So it’s still a pretty impressive result, but it suggests the importance of, I think, following these patients. And it may be that somehow brentuximab vedotin modulates some of the early toxicity, perhaps by suppressing graft-versus-host disease. But I think it’ll be very important to follow this cohort and look at what some other experiences are in some less selected patients. And my hypothesis is, we’re going to see that the outcome of allogeneic transplant remains somewhat questionable in patients with relapsed Hodgkin lymphoma.
I’ll just comment, if I could, on the duration of therapy question. The study that was done was a 16-cycle, or 1 year of treatment. And again, in a patient who achieved CR, those third of patients who achieved CR have very long progression-free survivals. And in fact, in the original study of about 100 patients, there are somewhere between 12 and 15 of them who remain in remission at least 2 or 3 years plus later. And almost all of them had achieved an early CR.
So I think the question is, an allogeneic transplant clearly needs to be discussed. But if the decision is made not to do an allogeneic transplant, some physicians stop after a CR. And some physicians would continue treating. My bias has been, in this situation, to continue treating with brentuximab vedotin for the 1 year, because I don’t think we know yet what the optimal duration is. And we do know that there are subsets of these patients that do achieve very long responses. And without a lot of good salvage options, I want to give people their best chance.
DR LOVE: Any situations, particularly older, comorbidities, a situation where you’d want to try to use B vedotin earlier, like up front?
DR FRIEDBERG: Yes. We’re participating in a clinical trial that is looking at brentuximab vedotin as monotherapy for the older, frail patient population with Hodgkin lymphoma. This is a pilot study. It does allow radiation. So if the patient has early-stage disease, you can give radiation. And it’s really asking the question, in a group of patients where we know that ABVD is poorly tolerated and the outcomes are very poor, can those patients benefit from monotherapy with this antibody drug conjugate?
So we were comfortable participating in that study, anticipating that for the uncommon patient who presents over the age of 70 with Hodgkin lymphoma, we would offer them participation in the trial. Outside of a clinical trial, I would not be comfortable doing that right now. But I think that in the older, frail patient population, I’d have a low threshold of doing what Mike did in his patient, where if they weren’t tolerating treatment well, quickly moving to brentuximab as second-line treatment.
DR LOVE: Julie?
DR VOSE: So in the up-front setting outside of a clinical trial, I would not use it, wouldn’t be able to be paid for. But certainly, if a patient shows us early on that they can’t tolerate the therapy, then it’s second nature. It’s already a second line, so I think that’s fine.
And definitely we use it for a bridge to transplant. Yes.
DR LOVE: Mike?
DR WILLIAMS: I agree.
DR EVENS: I think the question is maybe more second line than first line right now. I don't know how anyone feels about this. I haven’t adopted that, in other words, versus as a bridge to auto, so to speak, versus the typical ICE or ECHOP that we use to gain remission and on the road toward an autotransplant. Has anyone jumped on that ship yet?
DR VOSE: There’s a new trial that’s just opened up, that’s a little bit different. It’s a combination of B-vedotin and bendamustine as a bridge to autotransplant. And then the patients get B-vedotin after the transplant for a consolidation. This is for high-risk Hodgkin’s patients.
DR EVENS: Yes, and there are 2 other studies. Memorial has a study of sequential brentuximab vedotin followed by ICE, where City of Hope is doing single-agent brentuximab vedotin. I don’t know if he presented that at Lugano or not, Richard Chen. But yes, off of a trial, I wouldn’t, even in second line, much less first line right now, until there’s more data, more mature data. And we’ve already shown and discussed several examples where you have to be cautious of automatically moving these drugs to front-line therapy. You have to be cautious with toxicity.
DR FLOWERS: Yes, and I think it’s very challenging to know how and when to stop therapy and how to collect stem cells after B-vedotin and how much of a gap is safe, a safe gap, to give in between the autologous transplant.
DR LOVE: Jonathan, maybe you can comment on a couple of papers from Lugano, one by Moskowitz.
DR FRIEDBERG: Sure. First author is Allison Moskowitz. This is really the trial that Andy was just referring to, where they came up with a scheme of taking patients who had relapsed Hodgkin lymphoma, initially gave them brentuximab vedotin, then did a PET scan. And if the patients achieved PET negativity — I’ll come back to the definition of that in a minute — they immediately went on to their version of an autologous transplant. If they were still PET-positive, they went on to augmented ICE followed by transplant.
And the bottom line was, in about a third of the patients, they were able to go on to the autologous transplant without any chemotherapy after only 2 cycles of the brentuximab vedotin.
Now, the definition of PET negativity here was a very conservative PET definition. You had to achieve a Deauville score of 1 or 2. So many of these studies, when we talk about PET negativity, allow a Deauville of 3. So I think that’s why it was only a third of patients that were able to go on.
The other point to make is they only got 2 cycles of the brentuximab vedotin. So this and in the group who did go on to autologous transplant, there were no issues of stem cell collection and no issues, apparently, of toxicity. So this is still early, but this is the type of experience that may evolve to allow many patients who relapse with Hodgkin lymphoma to avoid the salvage chemotherapy in favor of earlier use of brentuximab vedotin.
DR LOVE: Any comments, Chris?
DR FLOWERS: I think this is potentially an attractive and exciting approach to be able to avoid chemotherapy. I’d like to see longer-term follow-up on these patients to know how these patients proceed in terms of maintaining relapse-free survival after not receiving chemotherapy to induce the remission.
DR EVENS: The only subtext I would add — I agree with Chris in terms of longer follow-up — is this Deauville criteria, that we’re using it a lot now. I think it’s important for the community practitioner to know the differences between that. As Jonathan mentioned, the most common cut point is at 3, which is background greater than the liver, whereas 2 is the mediastinum. And obviously, it factors into the balance of patients, if you have that higher cut point, so to speak, at 2. You will have more positive patients. But for most entities, advanced-stage Hodgkin lymphoma and others, it’s a cut point of 3. In other words, you have to have uptake greater than the liver.
And so when we talk to our nuclear medicine doc, we’re not asking him so much now in terms of SUV. It’s, is the uptake greater than the liver? Because obviously, there’s inter-PET, intra-PET variability between patients. So it’s important, at least, to somewhat standardize that.