Hematologic Oncology Update, Issue 1, 2016 (Video Program)Updated results of the Phase II SWOG-S1106 trial of R-hyper-CVAD versus BR followed by ASCT for MCL
4:19 minutes.
TRANSCRIPTION:
DR LOVE: So I want to ask you about another paper that was presented at ASH, an Intergroup study. I always thought this was a really interesting study to start with, which was pretransplant use of R-bendamustine versus R-hyper-CVAD. It actually ended up getting closed, but they did present some data at ASH. Can you kind of talk about the background of the trial, what happened with the trial and then the data that they reported? DR LEONARD: So the idea of this was to really compare R-bendamustine versus R-hyper-CVAD followed by autotransplant as initial therapy for mantle-cell patients and particularly younger patients. And one of the endpoints of the study was mobilization of stem cells. And so I think the bias of everybody going in was that R-bendamustine is an older-person’s regimen — it’s not going to be that effective — and R-hyper-CVAD is a younger-person regimen. And all these groups had used it pretransplant and had good results and shown great curves so that that was clearly going to be the winner. I think we were all surprised when there were significant rates of mobilization failure with R-hyper-CVAD suggesting that really in the real world that mobilization was a problem and, therefore, a significant number of patients couldn’t go on to get their transplant appropriately. And that, we know, is an issue with hyper-CVAD, is that it is profoundly myelosuppressive. There are people who have cytopenias and even MDS sometimes after it. But to have that documented as being such a common occurrence, I think, was a little bit surprising to everyone. So the other thing that came out of that, which informs our next set of trials, is that BR also gave high rates of minimal residual disease negativity. And so we’re learning that MRD negativity correlates with better outcomes. And so I think our next generation of trials in the cooperative groups is really going to be focused on how can we get the most patients to MRD negativity? And then for those, once we get people in remission, if they’re MRD-negative, can we get rid of the transplant? If they’re MRD-positive, can we make the transplant better to try to convert them into longer-term remitters? So I think MRD is going to be an important endpoint in our future mantle-cell lymphoma studies. DR LOVE: I think it kind of looked like the incidence of MRD and the responses, in general, were similar with BR to R-hyper-CVAD. DR LEONARD: Right. DR LOVE: Why do you think that was? And how much R-hyper-CVAD actually ended up getting delivered as opposed to being held? DR LEONARD: Yes. I would say that there were a fair number of patients that didn’t complete the regimen. But you’re right. I would turn that into the idea that BR gives you such high rates of MRD negativity, why would you want hyper-CVAD if you could get the outpatient regimen? But I think our next generation of studies is going to be really focused on comparing, just like these 2 were compared, comparing a couple of different regimens with novel agents to see what gives you the best MRD-negative rates. And then, can you get away with leaving out the transplant? DR LOVE: I always thought this was kind of an interesting trial to get an informed consent to, because it’s kind of different in terms of what you might expect in terms of toxicity. When the trial was designed, was there any thought about doing R-benda followed by transplant versus just R-hyper-CVAD without transplant? DR LEONARD: I think there was thought. And I think in developing these trials, as you know with treating mantle-cell when you’ve polled experts and you get your panel of responses, trying to get 10 people or even 3 people to agree on a regimen is tough. But yes, I think a lot of people had thought that you don’t need to do the transplant if you do hyper-CVAD. So I honestly think one of the results of this study is that we’re moving away. I think people are starting to look at the benda/rituximab plus ara-C combinations. And I think that may be something that we in the US explore further going forward as have the Europeans. |