Joshua Richter, MD: But I want to veer off for 1 minute because there's 2 studies that you both mentioned. You mentioned SWOG S0777 [NCT00644228], you alluded to MAIA [NCT02252172], so VRd [bortezomib/lenalidomide/dexamethasone] versus Rd [lenalidomide/dexamethasone] for transplant- ineligible DRd [daratumumab/lenalidomide/dexamethasone] versus Rd for transplant-ineligible. And yes, we’re all going to transplant lot of people. But let’s switch to [those who are] ineligible, those that we’re just deciding, we may collect but we’re not doing it. And I’d love to know anyone’s thoughts about, does everyone get VRd or VRd lite, as was published by Dr [Elizabeth] O’Donnell [MD] or are they getting a MAIA-like regimen? Any thoughts?

Alfred L. Garfall, MD: For the real transplant-ineligible population, the MAIA study provides really high- level phase 3 evidence—safety, long-term overall survival benefit—over Rd and a real ease of administration. And, so, I think that is my preference for the true transplant-ineligible population. Although, again, you have to look in real time at how patients are doing if they're not responding well. Some patients really do need a proteasome inhibitor. And I have patients that I have started on DRd who have really kind of lackluster responses and you would like to reduce the dose of Revlimid (Rev) [lenalidomide], but you can't because they're not in a good enough response. You add on the proteasome inhibitor and everything just melts away. So, you do need some real-time decision-making there.

Elizabeth O’Donnell, MD: You said exactly what I was going to say. You can't dispute the MAIA data, it's phenomenal, and that it's a great standard of care for this population. However, there are those patients who need the proteasome inhibitor. And it's nice to be able to have the flexibility to adjust your therapy based on what you're seeing. And unlike the transplant-eligible population, we do want to get the greatest depth of response and we know we can. And so that's a clear picture, is we can achieve MRD [minimal residual disease] negativity in transplant-ineligible patients even if they're not getting a transplant. That has to be the guiding principle as you treat, particularly in the frontline setting.

Susan Bal, MD: I was going to say, and when we look at the SWOG SO77 data, I think it's really helpful to think through the age of that population. The median age was so much lower, 63 versus 73 for the DRd. And when we looked at the benefit, most of that was coming from the younger patients. So, in our practice, I'm sure there's patients that do find benefit from proteasome inhibitor. But looking at the SWOG data and looking at where that benefit mostly came from, the DRd data supports a monoclonal antibody-based induction in most patients.

Natalie S. Callander, MD: I'm very interested in the French study that was presented at ASH [American Society of Hematology] this year. Now, going to dara-Rev-nodex, that their data, obviously, they just presented, I think just 12-month follow up, I think. But it really looks great. And we, I'm sure we would all agree dexamethasone is a real problem in our elderly patients. Even if it's 20 mg a week, it's a problem. So, I was very excited looking at that data that it looks good. Andthat may be our next new standard for elderly non–transplant-eligible patients.

Alfred L. Garfall, MD: Also, a problem in our nonelderly patients. I look at every chance I can to get rid of the data.

Elizabeth O’Donnell, MD: Cut it quickly.

Joshua Richter, MD: We've talked a lot about quads and triplets and Susan, I'd like to ask your thoughts, are there still patients out there that just get a doublet?

Susan Bal, MD: There are, and we all see them even in our practice, the most frail, the very elderly. There are patients who are over 85 or 90 years of age that present that are still well enough to be treated. And in some of those patients, I think a doublet is reasonable. And that helps you establish as a stress test, if you will, if they could handle a triplet. And sometimes I have started with, mostly, many times, due to availability and rapid ability to get the lenalidomide, but you've started them on daratumumab with dexamethasone, and then added in the IMiD as you're able over time. And we've been amazed at the responses that we've seen just with that doublet itself and [it] enables quality of life for these patients. So, yes, in thevery frail, the very elderly, there's still a small but real role of a doublet.

Elizabeth O’Donnell, MD: And, as you said, the goal is you start with a doublet, if it's a sick patient, if it's a frail patient. And if you can build in, and I agree with you that dara-dex is a very nice combination. It's well tolerated and you see surprisingly good results.

Alfred L. Garfall, MD: And sometimes you're getting back to the doublet, too, even if you get to the triplet. Patients either want to remove the lenalidomide [Revlimid] or maybe remove the daratumumab if they're handling the IMiD well and don't want to come in. And, so, you have that flexibility, if you get a good response.

Natalie S. Callander, MD: And living in a state in the US where we have a big rural population, sometimes an oral regimen is what you're going to have to do in terms of logistics. They [patients] can’t come in weekly for the first couple of months for daratumumab.

Joshua Richter, MD: I even have a few patients where they were older but also had significant respiratory issues where I started with bortezomib [Velcade] [and] dexamethasone. And I know it's a bit of an older approach, but Velcade, to me, has been the Swiss Army knife of myeloma. You can use it with anything weekly, every other week. Doesn't matter.

Elizabeth O’Donnell, MD: And it's easy to give. People take it so well, but if we look at the recent publication on the, my idea of looking at frail patients, what you see is that, yes, there were patients who had to come off study more so than the younger patients, but they derived the same benefit. So, when you looked at the 2 arms and you saw the triplet versus the doublet, the benefit was preserved. So, it should encourage us that we can give these triplet combinations in frail patients as well.

Joshua Richter, MD: And a point that both Natalie and Al made about the dexamethasone [dex] [Alessandra] Larocca [MD, PhD] published, to me, [is] one of the most important studies in recent years comparing Rev[limid](Rev)/dex, continuous versus Rd-R Rev/dex for 9 months, then dropping the dex and dropping the dose of Rev to 10. So, I think, one of these, you know, these new drugs allow us to do is we don't have to give Rev 25 and dex 40. You can give Rev 10, dex 12, and add Velcade, or dara[tumumab] and get some great outcomes.

Alfred L. Garfall, MD: I would love to see some more studies to just get rid of the dex entirely from the beginning. It's going to take some time, but as we incorporate more immunotherapy in the early lines of therapy, as we appreciate that even the drugs that weren't devised as immunotherapies actually have immunologic components to them, like the IMiDs, dex just cannot be helping with the immunologic effects.

Elizabeth O’Donnell, MD: What I explain to patients because when, especially when patients don't want to come off drugs necessarily, but when you think about the history of, of dexamethasone for myeloma, you talked about before we had terrible drugs. And so, dexamethasone was given 40 mg, 4 days in a row. And the study that determined the dose that we currently used, which is still high dose, was high dose vs our quote low dose. But there's never been a study of what, there's no dose escalation. There's been no phase 1 study of dexamethasone and multiple myeloma, [at least] not to my knowledge. And so, I don't think we even know what the right dose is, or the minimal dose is. So, we're, we're de-escalating, but we never escalated to know what the appropriate dose was to begin with.

Transcript edited for clarity.