DR LONIAL: The IFM DFCI trial, in which all patients received RVd induction. And the main study question was early transplantation versus late transplantation. All patients received equal amounts of therapy. All patients were — in the French version received 1 year of lenalidomide maintenance, in the US version received lenalidomide maintenance until progression.

And what we know from the French version of this trial with limited-duration maintenance is that the progression-free survival clearly favored the use of high-dose therapy and transplant. Overall response rate favored high-dose and transplant. Overall survival was similar between the two.

Now, you’d asked me earlier about MRD negativity. What’s really interesting about this is, if you look at patients who achieved 10^-6 negative MRD — so next-generation sequencing — it didn’t matter whether they had a transplant or not. Their progression-free and overall survival looked the same. For everybody else, it did appear to favor the use of transplantation, at least the progression-free survival. Overall survival was really short to see follow-up.

DR LOVE: And I guess the other thing about that, as you pointed out, the 1 big difference between the 2 trials was the maintenance.

DR LONIAL: Yes.

DR LOVE: And I guess — do you have any idea when we’ll see the North American data? And are you expecting that maybe there’s going to be less of a difference because the maintenance is more effective?

DR LONIAL: So that’s a really interesting question. And the trial is just about to complete enrollment, so it’ll be a few years before we see the data from that trial presented, just to give reasonable amounts of median follow-up. What really — and I’m a proponent of continuous maintenance in the post-transplant setting. But what I was really struck by was the fact that those patients who achieved 10^-6 MRD, their outcomes with only 1 year of maintenance was amazing. And that’s much better than I would have thought before. And it makes me wonder a little bit about is there an endpoint at which I would say that’s enough in terms of maintenance therapy?

DR LOVE: Because I know initially, when the maintenance data started coming out, people were saying, “Maybe you don’t need to do it with patients who are in complete response.” And then I guess there was enough data to support doing it. But now you’re talking about the same concept, except using MRD as a measure.

DR LONIAL: Yes. Yes. Yes. No. And I think that it’s really important data, because it may speak not just to quality of life and cost of therapy. I mean, if we’re going to talk about quadruplets as induction therapy, in my view the only way we can make that argument is if we don’t give continuous maintenance — if, at some point, whether it’s 1 year, 18 months, whatever it is, we say, “Patients that have achieved this benchmark, we’re stopping therapy,” because otherwise it’s hard to justify the 4 drugs.

DR LOVE: Any reason to believe that some of these people might be cured?

DR LONIAL: Absolutely. Absolutely. I mean, we know before maintenance therapy became the norm that there were about 10% to 15% of patients that were cured after high-dose therapy and transplant. And I’m defining “cure” as 12 to 15 years post-transplant, continuous complete remission, no maintenance. So the only way we’re going to know if that’s the case now and if that number has grown is by taking a bit of a leap and seeing how they do.

DR LOVE: In general, what’s it like to say, “We’re either going to do a transplant or not”?

DR LONIAL: The way that I think most of us have framed it is that it’s not a yes or no question — it’s a when question. And we know from historical trials from the French retrospective data series, from our group and others, that if you ask the question about timing of transplant, it’s hard to show that survival is necessarily impacted.

So what I would tell patients is, we know that early versus late, at least from the data we have, that the survival looks somewhat similar and so you’re not limiting your survival. And you’re answering a really important question in the context of how good are these new therapies.

DR LOVE: Just out of curiosity, in these studies, these 2 studies, what fraction of patients are actually getting transplanted on initial relapse?

DR LONIAL: So in the French analysis, I don't know the answer to that. In our series, everybody that has progressed on the observation arm, the delayed transplant arm, has gone on to a transplant.

DR LOVE: And what do you do about maintenance after this delayed transplant? Same approach?

DR LONIAL: So if they — basically, by definition they’ve progressed on lenalidomide if they’ve progressed in a delayed transplant setting. And so the discussion we have with them is either pomalidomide as maintenance or ixazomib as maintenance, going back to something different.

DR LOVE: So that’s not prescribed in the protocol?

DR LONIAL: No. Protocol stops once they relapse.

DR LOVE: As long as we brought this up, we’ve had a number of cases presented to us by docs in practice of people who had delayed transplant. Here it’s part of a trial, but we hear about cases. The patients are reluctant, and then they change their mind. And then they want to go on to have a transplant. How do you approach the issue of maintenance there when the transplant’s occurring down the line? They might have had multiple therapies.

DR LONIAL: Yes. I mean, I look to see what treatments they are still sensitive to. And I try and pick something that I can convincingly that I can give in the long term. Giving a medicine once or twice a week intravenously is not a long-term maintenance strategy. And so I try and think about what I can pick amongst their drugs to be able to do that.

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