Andrew P. Dalovisio, MD: I think that’s a good segue. Once you decide somebody’s transplant ineligible or they don’t want a transplant, I think there are a number of regimens you can use. I don’t think there’s necessarily a standard of care, although some may feel that way. A few of the regimens I’ll mention, as I said, if they say they’re super fit, or just don’t want a transplant, you can still talk about doing either just, it’s like standard-dose VRd [lenalidomide, bortezomib, and dexamethasone] or dara [daratumumab]. There’s another regimen called VRd-lite that I used to use a lot more now that I use DRd, [daratumumab, lenalidomide, and dexamethasone] where it was just VRd, but it extended the cycles out to 35 days [and] reduced the dose of the Revlimid [lenalidomide] and the steroid. That showed really good efficacy. We even saw some thought leaders adding daratumumab into that regimen, even though it’s off-label [use]. And don’t forget about the Rd [lenalidomide and dexamethasone] regimen. If you look at those studies, [the] 2-year PFS [progression-free survival] from just [Revlimid/dexamethasone was] 74%, and the overall survival [OS] rate was still 91%. So there are still some scenarios where we’ll have a 90-year-old–plus patient who doesn’t want to come for infusions or treatments. I might say Rd is a very reasonable thing to do.

Thomas Atkinson, MD: I started somebody on RD about a week ago. I think it’s very well tolerated even for extremely [elderly patients].

Kelly Pippin, MD: And we shared that a 90-year-old patient in a very similar situation who walked into the clinic feels very good, but has myeloma that was incidentally found, and he has some options that can keep him at home but probably halts some of the disease.

Thomas Atkinson, MD: Right. Sometimes just keeping somebody at home is adding so much more to their quality of life, and having that is really nice.

Kelly Pippin, MD: Talking about doing intense regimens, how many times have you had a very fit patient who you really want to do an intense regimen, but they’re like, “Hey, I have my spouse who has Alzheimer [disease] at home, I need an oral-only regimen.” That’s certainly come up before.

Thomas Atkinson, MD: That’s the reality of community practice, for sure. There are a lot of things that prevent the ideal scenario from happening, and you have to work with what you’ve got, basically.

Kelly Pippin, MD: Right. Exactly.

Ryan P. Griffin, MD: Andy, our internal algorithms talk about dara-Rd [daratumumab, lenalidomide, and dexamethasone]. Do you have more complications with Velcade [bortezomib] in our frail patients? Is there a trend to try to get away from Velcade?

Andrew P. Dalovisio, MD: With bortezomib, I think, generally, older people over 70 have a higher signal for peripheral neuropathy. Neuropathy risk is higher, they have renal inefficiency, also often have diabetes, and things like that. So I’ve generally tried to stay away from Velcade in people [aged] over 70 [years]. But I would say not religiously by any means. And that’s one of the reasons I do like the daratumumab-based regimens in these populations. I can segue into the MAIA study [NCT02252172], which I think established a standard of care arguably for these transplant-ineligible patients. What this did was it took transplant-ineligible patients who had an ECOG [performance status] of 0 to 2 and preserved renal function, about 750 patients, so [it was] a good-size study. And [randomly assigned patients] get DRd until progression or just Rd. That trial has been going on for a while, and they just updated the data at the most recent ASH [annual meeting of the American Society of Hematology] in December, ending with a median follow-up of 64.5 months. In the triplet arm, the median PFS was 62 months. So a little over 5 years vs just 34 months in the Revlimid/dexamethasone arm. And then at a median follow-up of 73.6 months, the DRd median OS wasn’t even reached, where it was 64 months in the Rd. To answer your question, Ryan, they did do a toxicity analysis, and there was a little bit more toxicity when daratumumab was added, but the rates of grade 3 toxicity were almost the exact same. Most of these adverse events you’re getting are mild cytopenias, nausea, infusion site reactions, and things like that [which] are very manageable, so really it didn’t add much toxicity. When I think of this regimen, when I have somebody who is 75, 80 years old—say they’re still [at a] relatively good performance status if they’re standard risk and in relatively in decent shape—I can say, look, two-thirds of people in your shoes are still alive 5 years from now…. Most of them are coming for just 1 injection once a month and [take] the rest of their pills are at home. So to me, this is a very palatable regimen, and I’ve had a lot of success with it. Interestingly, they also looked at a subset analysis of extremely frail patients. I can’t remember exactly how they defined it, but they didn’t call them not fit, but frail and not intermediate. And those patients actually still had a 3- to 4-year progression-free period on this DRd regimen. So even your older frail patients can stay on this and do well. Obviously, they don’t do as well as, say, your fit older patients, but they can still do really well on it. I’ll maybe put it to [the panel]; do you have a go-to transplant-ineligible regimen you use?

Kelly Pippin, MD: I think this is a compelling argument to do triplet therapy, even in really ultra-frail patients [for whom], at the eyeball test, we may be a little bit nervous to do a triplet therapy. And maybe there’s part of a comfort blanket in doing a [2-drug] regimen, thinking they’re very frail, [we] will be very easy with them. But I think this is compelling data to say let’s go for triplet therapy, even in these very frail patients.

Andrew P. Dalovisio, MD: Sure.

Ernest C. Quintin, MD: I can tell you, I’m a lot more comfortable with [daratumumab] in the subQ [subcutaneous] formulation. I remember when it was the IV [intravenous] formulation, you were going to get called…

Thomas Atkinson, MD: …getting called to the infusion center every time.

Ernest C. Quintin, MD: Yes, so now with the subQ…I haven’t really had too many problems with the subQ, so it really has just changed things.

Thomas Atkinson, MD: …It is very convenient.

Andrew P. Dalovisio, MD: We start with subQ now. We don’t even do IV for the first dose; we have been doing that for a while. And if they’re having no reaction by the third cycle, we just stop premedications. So it’s like a shot and they go. And the other thing is, like for amyloid patients or patients with heart failure, things like that, they don’t get the volume that they get with the IV. So I love it, I think it’s a great addition to the armamentarium. A couple of other things I would say about the MAIA trial, we talked about frail patients who can still do well, but there have been a couple of subset analyses that have come out where they followed patients who came off of Revlimid [lenalidomide] due to toxicities and were just getting [daratumumab] monotherapy. They updated some 3-year data and showed that if the patients could stay on the Revlimid for 12 to 18 months, almost all of them were still progression-free on single-agent [daratumumab] at 3 years. So it gave me a little bit of ammo to say, if a patient’s really struggling with Revlimid, if we can just get through a year or 16 months or 18 months, you can do really well just on single-agent [daratumumab]. And then they also did another study where they just dropped out the [dexamethasone] completely, and this patient seemed to be doing just as well. I generally try to stick to the 3 drugs as studied, but it gives you a little bit of ammo there to say you can drop the Revlimid or drop the [dexamethasone] out at a certain time point if they’re really struggling, which can certainly happen with these older patients.

Transcript edited for clarity.