DR LOVE: A couple more papers, Noopur, that, as we looked back over the year, seemed to really have a lot of effect on people. Again going back to the ASH 2015 meeting, the study by the IFM group looking at transplant and the complementary work that was done on minimal residual disease. Again, can you just kind of provide an overview of what that data set demonstrated and what you think it means?

DR RAJE: Sure. So this was in the obviously transplant-eligible patient population. And the question here was now, in the context of all of these new drugs, what is the place of an autologous transplant? And the way this study was done was patients who were transplant eligible were collected and then half randomized to getting the stem cell transplant. The others continued the triplet combination of RVd, followed by consolidation and followed by maintenance.

And what was seen in this data set was the fact that progression-free survival and response rates favored high-dose therapy, so autologous transplant tended to do that. If you look at the overall survival in this patient population, there was really no difference.

And what was really quite nicely done by Hervé Avet-Loiseau here was looking at MRD in this patient population. And what he showed very nicely is — and, again, this is not a big surprise — if you’re MRD-negative, you’re going to do better than somebody who has residual disease.

But the big take-home, for me, from this was it didn’t matter how you got to that MRD-negative state, whether it be with a transplant, whether it be with the consolidation and continuous therapy with RVd followed by maintenance. But folks who got to MRD negativity did well. So I do think the question of transplant, based on this data set, is, sure, transplant favors PFS, but if there are folks who get to that MRD-negative, can you then identify a subgroup within this patient population who may not need a transplant? And I think we need to wait on data.

There’s an ongoing trial, the DETERMINATION trial, which is happening as we speak.

DR LOVE: That’s the North American version of this French trial.

DR RAJE: That’s exactly right. And there are really important subtle differences — not subtle, actually. There’re very important differences here. And that’s to do with the duration of maintenance. And we have seen this in myeloma. The longer you stay on treatment, your depth of response increases.

The French trials have allowed for maintenance for up to 1 year, where the DETERMINATION trial and the practice in the United States really is once you’re on a maintenance, you stay on maintenance until progression.

So that’s something which we will see differences on. And we’ll see whether that continued maintenance allows the nontransplant arm to catch up to the transplant arm. We don’t have the data, clearly.

DR LOVE: So, Rafael, of course we’re looking for future research, but people have to make decisions today. Based on what we saw there, it seems like it might be a consideration. Maybe it wouldn’t be standard for a doc in practice to actually try to measure MRD and, if it were negative, say to the patient, “I’m not really sure you need a transplant.” First of all, if they wanted to do that, what’s the best way to measure MRD? And is that really outside the bounds of evidence-based oncology nowadays?

DR FONSECA: That’s a very, very tough question, I’ll tell you. I think it’s possible for someone to have that conversation, although I would argue that still, nowadays, the standard remains transplant and, in fact, the trial was not really designed to show that transplant was important. It was really asking the question, can you get away without transplant? I’ve already faced that situation. I had a patient, very smart individual, again, finished induction therapy and came to me after that for a second opinion after having received 4 cycles of VRd. He says, “Doctor, I don’t want to have a transplant. Is there anything we can do?” I say, “Well, guess what? I just saw this French abstract. Let’s measure MRD out of your bone marrow.”

We did it, and the MRD showed 1 copy out of a million. The patient was MRD-negative by flow, which goes to your second question. We can do it by flow cytometry or you can do it through a reference lab through next-generation sequencing. We’re doing it as standard of care for our patients that complete transplant, through the next-generation sequencing, although we do it at Mayo, too, by flow cytometry, even though we’re an academic institution. But I think it’s a fair question.

If I was a myeloma patient, I finished induction with a great regimen — let’s say I was going through a clinical trial and I got KRd or something like that — and I was flow- or next-generation-negative, I think I would think very hard about what am I going to do next. Now, I declare myself a fan for a transplant, but we’ll have these questions come up for the next several years.

Diagnosis and management of smoldering myeloma

Induction, consolidation and maintenance therapy for MM

Treatment of relapsed/refractory MM

Novel approaches under investigation for MM