Refining Systemic Therapy for Multiple Myeloma - Episode 6

Newer Regimens in Myeloma: A Need for Transplant?

Transcript: A. Keith Stewart, MB, ChB: So somebody alluded to this trial earlier, where giving 12 months of carfilzomib, lenalidomide, dexamethasone gave you the same MRD negativity rate as the same regimen with a transplant in the middle. The conclusion being that maybe the transplant wasn’t helpful. So what do you think about that? Are all MRD-negative patients the same, or?

Adriana Rossi, MD: If you can get to an MRD-negative state, how you got there is not as important.

A. Keith Stewart, MB, ChB: Maybe for the audience you can explain what you’re referring to.

Adriana Rossi, MD: So when we compared the lenalidomide, bortezomib, dexamethasone with transplant as a consolidation versus delayed, there was a PFS [progression-free survival] benefit but there was not an overall survival benefit. So I think there’s still some room for debate within the field. But when they did look at MRD negativity, regardless of which arm you were in, reaching that MRD negative state did give you a significant benefit. And so, data like that makes me, you know, lean towards hopefully getting to a place where MRD would dictate therapy and a change in therapy.

A. Keith Stewart, MB, ChB: Independent of how you get there.

Adriana Rossi, MD: I don’t think it’s ready yet. But, it’s my preference.

Faith Davies, MD, MBBCh, MRCP, FRCPath: The problem with all of those studies, though, if you don’t do the transplant, you’re waiting. And you don’t know which of your patients, upfront, are going to achieve the MRD negativity. There are far less that achieve MRD negativity without the transplant.

A. Keith Stewart, MB, ChB: Well you can always do a transplant at 1 year. There’s no reason not to do that, if you weren’t there, to be provocative?

Faith Davies, MD, MBBCh, MRCP, FRCPath: That is provocative, and I can’t currently think of an argument back. But I mean what you don’t want to be doing is treating for ages, waiting for this MRD negativity that never comes.

Thomas Martin, MD: I mean this is a perfect place for a clinical trial. Those that get induction therapy, whether it’s 4 or 6 cycles, those that achieve MRD negative status, you randomize them to just continue maintenance or to a transplant plus continue maintenance. This would be really great. But until we get there, we have enough trials that were transplant versus no transplant. We should look back at that and all of the people who are MRD negative in those arms and see how they did.

Rafael Fonseca, MD: You know, in the French study, and there was a recent publication in Blood in September, they looked at MRD. And MRD blows everything out of the water as a prognostic factor. We see hazard ratios of 0.2-something. I mean we don’t see that with any other prognostic marker. It actually can break, depending on the treatment arm. It can segregate prognosis based on whether you’re standard risk, or high risk. So I think that particular paper has set the standard for how we think of that, not only as we monitor patients, but also as we design clinical trials in the future.

A. Keith Stewart, MB, ChB: So transplant can go away if you’re MRD negative, or not, Tom?

Thomas Martin, MD: I would say for me it’s a much longer discussion with the patient who’s MRD-negative, and I’m talking about, do we do a transplant or not? And I kind of talk with the patient. And I’ve had patients who are MRD negative not go forward with the transplant. We’re going to delay.

A. Keith Stewart, MB, ChB: So on Friday a colleague made the same argument. At Memorial Sloan Kettering, that’s sort of the philosophy now. If you’re MRD negative you give them the option.

Faith Davies, MD, MBBCh, MRCP, FRCPath: No, I’m not there. No, because I’m going to argue back here. I’m going to say that the patient who is MRD negative is actually the one I could potentially cure. And so, maybe they are the one I should be transplanting because I may never get into needing relapse.

A. Keith Stewart, MB, ChB: I think I’m in your camp still. I mean I’d love to get rid of transplant, but it still feels to me like it’s not that toxic and it seems to be fairly beneficial in terms of deepening response. So even if it’s subclinical and it’s MRD negative, those people still relapse often. They’re not cured at that point.

Rafael Fonseca, MD: But there’s some serious flirting that the transplant will be dispensable. I am in your camp, and I think your point is excellent. There’s the unfairness across cancer that those that do well do better, and those that do bad do worst. And if you have that person

who’s MRD-negative, because, of course, you can only say there’s no evidence of disease... You cannot conclude that there is evidence of no disease. So maybe the transplant takes care of any residual cells, but obviously at the high price

Adriana Rossi, MD: So if you are going to use the word cure, and you’re going to say, “OK, I got you to a MRD-negative state and the transplant will get rid of everything,” are you still doing maintenance?

Faith Davies, MD, MBBCh, MRCP, FRCPath: I’m going to do the maintenance as well. I think one of the things the maintenance studies have shown us is that the MRD-negative patients still benefit from having maintenance. And I was going to say, I guess at this point I’d love to encourage the French to republish and let us know an update on their MRD-negative patients from their last study so that we could actually see what’s happening to them now 2 years later.

Transcript Edited for Clarity