Upfront Combination Therapies in Myeloma



A. Keith Stewart, MB, ChB: What about 4-drug regimens, Christina? Where do you think daratumumab and elotuzumab might end up in our practice? Maybe you could start by telling the audience about the trial that we’ll present here, looking at daratumumab in the frontline setting, if you’re comfortable with that.

Cristina Gasparetto, MD: Yes. Well, the 4-drug trial that is going to be presented at ASH is the ALCYONE trial, in the non-transplant eligible, where the daratumumab is added to the melphalan/prednisone/bortezomib (Velcade). And it is a phase III randomized trial, so patients are on the 4 drugs versus the 3 drugs. It looks like daratumumab impacted the depth of response and the PFS. It’s too early to say and on one of the critiques we were talking about earlier, unfortunately, the MPV arm of the therapy was discontinued after 8 cycles while on the daratumumab, but there was a continuation of therapy that probably impacted on the depth of response, continuation, and PFS.

A. Keith Stewart, MB, ChB: So, this is a very important study, we’ll just spend a minute on it here. Bob, your reaction to this VMP (Velcade, melphalan, prednisone) with continuous daratumumab versus VMP alone, do you think this will get FDA approval and be part of our standard of care or tell us how you interpret this?

Robert Orlowski, MD, PhD: I agree. The data are very positive, not unexpected, but VMP is not very popular here in the United States. There is an abstract from Andrzej Jakubowiak looking at KRd with daratumumab. It’s a single-arm study.

A. Keith Stewart, MB, ChB: That’s the first time I heard anybody pronounce his name perfectly. So, there’s Polish heritage there but go ahead.

Robert Orlowski, MD, PhD: Exactly. Yes, I’ve got a little bit of background there. But they had virtually a 100% response rate and a very high VGPR (very good partial response) or better rate. I think it was 80% to 90%. So, it’s certainly an active regimen. It would take a randomized study to try to see if it’s better than KRd or VRd. Actually, I like Hari’s approach, and I’ve done that on a couple of patients where we typically start high-risk and even standard-risk people on KRd. But if we don’t see a PR after 1 cycle, we think about adding daratumumab. And especially if you hit a plateau fairly early and you’re not at a complete remission, I think adding a fourth drug would be reasonable and that’s one way we can maybe reduce the financial toxicity, so that we’re not giving the 4 drugs to everybody up front.

A. Keith Stewart, MB, ChB: Thoughts on this important phase III trial, Noopur?

Noopur Suresh Raje, MD: So, again, I think most people have captured the limitations of the study that you have a standard of care arm, which has limited duration treatment. And I think what we’ve learned over the past several years now is continuous therapy should be the way to go in older as well as younger patients. So, with those caveats, I think everybody is covered…

A. Keith Stewart, MB, ChB: So, you think we’ll be using daratumumab up front soon?

Noopur Suresh Raje, MD: I do. It may not necessarily be with the VMP combination. The Maia study will be coming out and the readout for that.

A. Keith Stewart, MB, ChB: What is the Maia study for the audience?

Noopur Suresh Raje, MD: The Maia study is lenalidomide/dexamethasone with daratumumab compared to lenalidomide/dexamethasone alone, and we hope to see that data probably late next year.

A. Keith Stewart, MB, ChB: Hari?

Parameswaran Hari, MD, MRCP, MS: Yes, just as Noopur said. Then there’s the ongoing GRIFFIN study in the United States of daratumumab with RVd. The most popular triplet here is with daratumumab added as compared.

A. Keith Stewart, MB, ChB: It seems somewhat inevitable to me that daratumumab as part of a 4-drug cocktail will be part of the process. It is going to be financially difficult. Any solutions here? Any thoughts? You talked about maybe giving, you started with continuous therapy. What about giving shorter durations of therapy?

Noopur Suresh Raje, MD: One way of looking at it—because we have the diagnostic tools in place and we haven’t really gotten to MRD just as yet, Keith—with this MRD tool, one can imagine that if you use 4 drugs, you’re going to really deepen responses with depth of response. If you get to that MRD-negative state, you may be able to actually stop treatment after a fixed duration.

Transcript Edited for Clarity

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