DR MIKHAEL: The French Myeloma Network trials are remarkable, how they can just treat so many patients and evaluate so many patients in a very systematic, careful way. Their goal is literally every new patient with myeloma is placed on a protocol.

And again, they demonstrated the feasibility of giving carfilzomib/len/dex prior to an autologous stem cell transplant and in induction therapy.

Of course, there are a few more cardiac challenges. And it’s a little bit more inconvenient, by virtue of the twice-weekly IV administration. But this is, again, now a more systematic, larger trial that is justifying the use of carfilzomib front line.

The other study, of course, that was not presented but that we’re hotly anticipating results of probably this year is the KRd versus VRd, or carfilzomib/lenalidomide/dex versus bortezomib/lenalidomide/dex, the ENDURANCE trial that is based here in the United States comparing these 2 regimens together to see if there are significant efficacy and toxicity differences.

DR LOVE: And I think also there’s a maintenance question in the trial, right, 2 years versus — or what is it?

DR MIKHAEL: No. You’re absolutely right. So the trial was designed to answer 2 questions. The first was KRd versus VRd. These are in nonhigh-risk multiple myeloma patients. And then after the induction phase, patients are randomized to receive lenalidomide maintenance for either 2 years or indefinitely until such time as relapse.

Now, I think since then, we’ve gained more information in the lenalidomide maintenance world. And I would suggest that the standard of care is to give lenalidomide maintenance until relapse, as opposed to artificially stopping in 2 years. But this study will provide more information on that question.

DR LOVE: So I’m assuming the first shot at the data probably is going to look more at the up-front question and maintenance maybe will come later.

DR MIKHAEL: Absolutely.

DR LOVE: So I’m going to give you a chance to make your prediction. I have mine, but let me hear yours first.

DR MIKHAEL: I think the prediction is going to be that they’re not very different from an efficacy standpoint. There’s probably going to be a slight lead for the carfilzomib arm. But that will be balanced by the fact that there will likely be slightly more toxicity in the carfilzomib arm than in the bortezomib/len/dex arm. Now, I’m not a prophet. I’m just Joe. But if I were to predict, I think that we’ll ultimately see that they’re both legitimate options for patients and we’ll want to tailor it to individuals based on their risk status, potentially preexisting neuropathy, convenience and ability to get to the clinic. Ultimately, of course, we’re using more carfilzomib once weekly, which does help some of that convenience factor as well.

DR LOVE: But when you talk about tolerability, you’re talking about dyspnea and cardiac issues?

DR MIKHAEL: Correct, dyspnea, potential of tumor lysis, increasing hypertension, some of those things that we see with carfilzomib, although I think the overwhelming majority of those are overcome with careful use of carfilzomib. And we’ve been able to demonstrate that in our center, that if people are treated carefully with carfilzomib, the true rate of cardiac events, if you will, is less than 5%.

DR LOVE: Yes. I was going to say that — I mean, we’ll see. But I wonder whether really you are going to see a big difference in tolerability. But the thing that I will be interested in, I assume they’re doing MRD measurements. Do you think that’ll be reported?

DR MIKHAEL: Yes. I know that that was part of what was being captured. So we’ll have to obviously wait to see the depth of response between them.

DR LOVE: Because that’s where maybe I could see that they might see something. To see a difference in clinical outcome a lot of time takes a lot of patients and long follow-up. But I’d be really curious about what happens with MRD. Right now when you look at it indirectly, do you see any reason to believe that KRd would lead to greater MRD negativity?

DR MIKHAEL: I think it’s hard to know if it’s going to be that big a difference. Of course the challenge is, the comparator, VRd, is so good.

DR LOVE: Right.

DR MIKHAEL: So the law of diminishing returns, we’re getting lesser and lesser amounts of ability here to demonstrate a difference. But I think you’re very right to say that, that if there is going to be an efficacy difference, we’ll probably see it in MRD before significant differences in response rates or PFS.

Up-front management of newly diagnosed multiple myeloma (MM)

Management of relapsed/refractory MM

Smoldering myeloma and primary amyloidosis

Non-Hodgkin lymphomas

Hodgkin lymphoma

Chronic lymphocytic leukemia

Acute myeloid leukemia (AML)

Myelodysplastic syndromes (MDS)

Myelofibrosis