Elotuzumab and Ixazomib in Multiple Myeloma

Transcript:Keith Stewart, MB, CHB: So we did talk about the ENDEAVOR trial. I want to move on. This meeting last year, then two trials of this meeting have done triplet therapy with lenalidomide-dexamethasone as the backbone, and either carfilzomib in the ASPIRE clinical trial, elotuzumab in the ELOQUENT trial, or ixazomib in the TOURMALINE trial. We have the principal investigators of all these trials here I think. So, we should be able to cover this pretty well. Let's talk about those, just a quick snapshot of all of them, and then, when would you use one and when would you use another? So let's start with the ELOQUENT clinical trial because, Ajai, you've mentioned that already.

Sagar Lonial, MD: So ELOQUENT-2 was a randomized trial of elotuzumab plus lenalidomide/dexamethasone versus lenalidomide and dexamethasone, in a 1-to-3 prior lines of therapy patient population. What we know about ELOQUENT-2, as reported at ASCO this year, is that the progression-free survival was about 30% better than what you'd see with lenalidomide and dexamethasone. And that about a third of the patients in that trial met what we would, through the IMWG, consider to be high-risk disease by genetics. And genetics in this trial was done centrally.

My perspective of the take-home messages from that trial are that in the subgroups of 17P and 414 translocation, there is a significant benefit for the addition of elotuzumab over lenalidomide/dexamethasone alone, and that for equal response, PR versus PR, if you got elotuzumab, the durability of the PR was longer than if you didn't get elotuzumab, and the same for VGPR or better. And that actually has not been shown in a randomized trial before.

Keith Stewart, MB, CHB: Excellent point. So elotuzumab added to RD clearly an advance, improvement progression-free survival, prudent time to progression.

Sagar Lonial, MD: Yes.

Keith Stewart, MB, CHB: We're waiting for some survival data.

Sagar Lonial, MD: Correct.

Paul G. Richardson, MD: But there is a trend and the important point, I would echo Sagar's points, the other thing is it's a very well tolerated antibody, and it has a very convenient infusion schedule, which I think for practicing oncologists is a very relevant point.

Keith Stewart, MB, CHB: How long is the infusion for elotuzumab? I haven't used it a lot.

Sagar Lonial, MD: So the first few days, those are probably around three to five hours, somewhere in that ballpark. But there is an accelerated 60 to 90-minute infusion as well, once you get past the first few doses.

Paul G. Richardson, MD: Sagar's quite correct, it's about three hours to kick off with, and then you can taper right down and basically once you're beyond cycle 4, you can be out about an hour, an hour and a half.

Keith Stewart, MB, CHB: We'll probably come back to the infusions in a minute. Ixazomib; TOURMALINE trial

Paul G. Richardson, MD: Again, it's been an incredible year in our world, I think. And I think the ixazomib data, which will be presented by my colleague Philippe Marrow at the meeting, is really remarkable. It's showing a six-month progression-free survival benefit in favor of the three drugs versus the two. And I think the thing that's very interesting is, a couple of things really. One, the tolerability of this approach has been excellent. There's obviously too early for maturity in terms of survival benefit. But to a point that Sagar made, the high-risk population are really being well addressed with this platform. And, again, the 17-P deletion subpopulation stand out, just as they did in ELOQUENT-2. I think that's very favorable.

One interesting thing about the TOURMALINE data is that the progression-free survival curves, whilst there's a response rate difference and all those things, they don't separate very early. It takes up to nine months before they separate. And I honestly believe that one of the reasons for that, I think there are a number of factors to the way the trial was done, it's a very real-world population. We allowed refractory patients and primary refractory patients into the group, so this confounds us a little bit. But I also wonder whether the once-a-week schedule of ixazomib is one of the issues here in terms of the rapidity of progression-free survival difference. Having said that, we're very pleased with the combination approach. It's clearly been very favorable.

Keith Stewart, MB, CHB: You may have said this at the beginning, but this is an oral proteasome inhibitor.

Paul G. Richardson, MD: Absolutely.

Keith Stewart, MB, CHB: With once-a-week bortezomib-based backbone.

Paul G. Richardson, MD: It is once-a-week.

Keith Stewart, MB, CHB: The ASPIRE Clinical Trial, which is a trial that I was part of, took lenalidomide, dexamethasone, as well, and combined it with carfilzomib of the label doses of 20 to 27 mg per meter squared. In that trial, the progression-free survival was quite long at 26 months, but interestingly enough, the lenalidomide arm of the trial also did a bit better than the other two studies.

However, what was impressive about the carfilzomib-lenalidomide-dexamethasone regimen was the depth of response was very high. One-third of patients entered a complete remission with this therapy. And I think some of us were concerned that by adding a third drug we might see a significant increase in toxicity. And, in fact, that proved not to be the case except in, as we've all discussed already, a very small percentage of patients who had some symptoms compatible with congestive heart failure, increase in hypertension.

Transcript Edited for Clarity