Considering Daratumumab-Based Quadruplets for Myeloma

Tramscript: Paul Richardson, MD: Sagar, if I may, to build on this, can you briefly summarize for us the constructs of when you’re adding DARA [daratumumab]? I think we’ve touched on a lot of this, but when you’re adding daratumumab to KRd [carfilzomib, lenalidomide, dexamethasone], the role of it in consolidation. What did you think of the various presentations from Ola Landgren, MD, PhD, and Luciano Costa, MD, PhD, in this regard?

Sagar Lonial, MD, FACP: I think there is no question that you again can get deeper responses. And the addition of daratumumab, I think we’re going to add a fourth drug to our induction therapy. It’s going to be a duration of therapy question because ultimately, in my mind, if we’re going to a quadruplet up front, one of the key metrics we need to be able to measure is when can you stop therapy. I’m all in favor of measuring and paralleling MRD [minimal residual disease] with PFS [progression-free survival] to answer that question. I’m not sure it’s going to be at 6 months. I think it may be a later time point, and what we know about MRD-negativity is it’s not right now, certainly at early time points, a surrogate for cure, which is where I think we all want to be. We all want to get there, but you may need more prolonged therapy to get there.

Paul Richardson, MD: Ken, I’m going to change gears again and say what are the quadruplets that appear to be promising?

Kenneth H. Shain, MD, PhD: Obviously we have isatuximab, KRd [carfilzomib, lenalidomide, dexamethasone] is going to come around. We’ve done now, others presented on IXA [ixazomib], RV [lenalidomide, bortezomib], DEX [dexamethasone] plus daratumumab.

Paul Richardson, MD: Yes, exactly.

Kenneth H. Shain, MD, PhD: These are all things I think really embrace all the options we have up front as you learn. Going back to the conversation we had earlier where how could we individualize therapy for our patients. Maybe an all-oral regimen and subcutaneous daratumumab is going to be something that’s really fantastic for individuals where that’s the right patient for the right drug combination. I think it provides us that information, we know now we can add this to any triplet we think might be important and get information, a monoclonal, whether it be daratumumab or even isatuximab.

Paul G. Richardson, MD: Nina, if I may, with the ixazomib, lenalidomide, dexamethasone, daratumumab in the non-transplant eligible patients, there’s a very nice paper from the Mayo Clinic group. What’s your impression of that regimen, recognizing a larger trial actually is about to launch in the Alliance trial group looking at this in a comparative fashion?

Nina Shah, MD: I think the main part of that, it has a nice response rate. It’s showing, we don’t have long-term data yet, as you know, but it’s very patient friendly.

Paul G. Richardson, MD: Yes, quite.

Nina Shah, MD: I think this is important because you do have to individualize patient therapy for whoever is coming, what can they do, and how frequently can they come. Because when daratumumab gets to be monthly, it’s not that hard. Now it’s going to be subcutaneous monthly, also not going to be that hard. Now you have an all-oral regimen for the rest of the month. That’s a lot more patient friendly. Neuropathy with ixazomib, probably less than the full dose of Velcade, not sure. It’s hard to know exactly. It’s pretty well tolerated, so I think this might be something that our patients who might be in the community, who want to come see us initially, but maybe want to back off after a while, this will be good for them.

Paul G. Richardson, MD: Excellent.

Sagar Lonial, MD, FACP: I do think in that ixazomib, lenalidomide, dexamethasone, daratumumab regimen, it’s an interesting regimen because you’re right, it is relatively easier for patients. I remember in the first presentation that I think Shaji Kumar, MD, said that the reason that the response rates do not look like what you’d expect for other triplets plus daratumumab is because they were using mass spectrometry, which means you’re not going to get CRs [complete responses] of the same frequency that you will….

Nina Shah, MD: We know it’s more sensitive.

Sagar Lonial, MD, FACP: I don’t remember whether that was in this presentation, but it may be an important caveat to make sure when you’re doing those illegal cross-trial comparisons.

Nina Shah, MD: Another variable.

Sagar Lonial, MD, FACP: But we know the numbers, because the number of patients are often not put on those slides, and we know the methods for assessment.

Paul Richardson, MD: That’s an excellent point, Sagar. I think from the presentation that it was clear though that the response rates are impressive, and their MRD assessments, and so on.

Transcript Edited for Clarity