Roundtable Discussion: Aliawadhi Explores Maintenance Therapy in Patients With Multiple Myeloma

Sikander Ailawadhi, MD

During a Targeted Oncology Case-Based Roundtable event, Sikander Ailawadhi, MD, consultant, Division of Hematology/Oncology, Department of Internal Medicine, and professor of Medicine at the Mayo Clinic, discussed maintenance therapy for patients with multiple myeloma.

AILAWADHI: We take into account the patient’s age, their fitness or frailty; performance status— [which] is extremely important—adequate organ function, concomitant with whether they have cardiac amyloidosis; and, very importantly, patient preference. That also brings into [question] the patient’s support system. Is the patient able to get to a transplant center locally or not, etc?

SAWHNEY: I didn’t vote for CyBorD [cyclophosphamide, bortezomib (Velcade), dexamethasone], but I have used it in a subset of patients who have renal disease. That’s where I use CyBorD. With fluctuating renal function, you can’t give them Revlimid [lenalidomide], and [although] I voted for VRd [bortezomib, lenalidomide, dexamethasone] I would say I don’t use VRd, I use VRd lite.

SHARMA: I agree. I use CyBorD in patients with renal insufficiency. Daratumumab [Darzalex] is not a bad option now, or DRd [daratumumab, lenalidomide, dexamethasone] in these patients, if you want to use that.

AILAWADHI: I’m glad you brought up DRd, because [no one voted for] DRd. Let’s say a patient is started on CyBorD. Would you keep them on CyBorD or would you after a few cycles consider switching them to either VRd or VRd lite, for the sake of [renal insufficiency]?

SAWHNEY: I do that with VRd. As soon as the creatinine level becomes normal or stabilizes, we go to VRd lite.

SHARMA: I would do the same.

AILAWADHI: Excellent. We end up doing that too, switching to VRd or VRd lite, whatever the case may be. Although there’s no head-to-head comparison, there are some data from a large prospective clinical trial suggesting that outcomes may be superior with VRd, so a PI/IMiD [proteasome inhibitor/immunomodulatory drug] combination does seem to be that good starting point.

We touched upon the treatment options, why we would consider one versus the other. DRd is FDA approved, so let’s not go to the quadruplets—daratumumab-VMP [bortezomib, melphalan, prednisone], etc—because we don’t use VMP in the United States.

AILAWADHI: Any thoughts around using DRd frontline, especially for transplant-ineligible patients? There is FDA approval there for frontline DRd.

SAWHNEY: It’s approved, but I don’t use it. I think a lot of my patients who are transplant ineligible have other comorbid issues. They’re on a lot of other medications. Revlimid is not an easy drug for elderly patients. [Also] from a cost point of view, [because] they have to pay for it, I try not to give them DRd. If I [must] use something, I may use the DVd [daratumumab, bortezomib, dexamethasone] regimen in front line, but DRd is more of a headache in my patient population, at least.

AILAWADHI: You mentioned you prefer to use VRd lite. Why would you use VRd lite but not DRd?

SAWHNEY: I could use DRd, but I haven’t found that regimen to be very appealing. I can’t tell you why. I’ve used it a couple of times. If I have to use daratumumab, then I may as well give Velcade rather than giving 1 pill and [having to] keep track of how many days the patient is going to take Revlimid.

My patient population is 75 to 80 years old or nontransplantable. At least with Velcade, I know when they come in, they get it. It’s a subcutaneous injection. It’s logistics more than anything else.

AILAWADHI: OK, fair enough. [Dr Nair], may I ask you what you would do differently or the same?

NAIR: Typically, I think we tend to do the standard VRd program, and we have to have some reason to switch to that daratumumab-based regimen. If there are some extenuating circumstances where one cannot get a drug for some reason, we will try to come up with the regimen that would fit that patient’s profile in terms of cost of logistics.

AILAWADHI: I think that’s reasonable.

SHARMA: I think in the practice setting, you have to look at a few other things. Most of these patients are on Medicare and we are in OCM [the Oncology Care Model]. You have to look at the cost perspective of all these regimens and try to be as uniform as possible. Also, with managed Medicare you have these tiers, and they send you feedback. I see the feedback coming [that says whether] you were in their “preferred” regimen pathway. They have their own pathways that they won’t even tell you [about]. But if you are there, and you are hitting those, they give you incentive. Again, it’s not about using it or not using it. These days there are so many of these regimens, especially for myeloma, and I can tell you right now for OCM, this myeloma just as 1 diagnosis is a killer, and because of this, it is very challenging for folks to take on 2-sided risk.

AILAWADHI: I’m glad we’re not having the discussion around the [recent] CAR [chimeric antigen receptor] T-cell therapy approval.

SHARMA: That’s interesting you said that. This is not that bad, because what happens is they then tease out that if a patient goes for CAR T, it’s an outlier; it comes out of the cost or it goes into the experimental section. I’m not worried about CAR T; I’m worried about these newer combinations.

AILAWADHI: If a patient is to start VRd or VRd lite, do you give a certain number of cycles of the triplet and then go to Revlimid maintenance?

SHARMA: I follow the clinical trial, although it was originally 8 cycles or so, and if the patient has reached stable CR [complete response] or VGPR [very good partial response], then I flip them over to [Revlimid].

NAIR: Typically, we will do 8 [cycles]; sometimes we can push the envelope to 12—and then do maintenance after that. It depends on the patient’s overall functional status and all these cytopenias that come with these medications. Usually 6 to 8—we rarely have pushed it out to 12.

AILAWADHI: How about the DRd [combination]? Dr. Nair, you mentioned you’ve used it in the frontline setting. In that setting, is the patient staying on DRd, daratumumab and lenalidomide [DR], or just lenalidamide?

NAIR: No. I tend to drop daratumumab after [approximately] 8 to 12 cycles and then keep them on maintenance.

AILAWADHI: I think that’s also interesting. There is a protocol that we have tried to get through NCI [National Cancer Institute] for cooperative groups trying to ask that question of DRd versus VRd lite for the transplantineligible frontline setting....Both are FDA approved, or at least VRd is, not necessarily VRd lite, and that kind of question does come up: Do both arms go down to Revlimid single agent or [should] one stay on just DR because that’s how the trial was done?

AILAWADHI: Although there is more category 1 evidence in this nontransplant eligible setting, if there are “real-world data” brought from [practice] databases, do you take those data into account and do you think those should be informing our practice? We know that the true frail, elderly patients are typically not even included in clinical trials.

SHARMA: I’ll tell you a big no right now—this whole realworld data showing retrospective analysis, controlling for Rd [lenalidomide, dexamethasone] [as in the PEGASUS study],1 no, [I am not]. I think until there’s a head-to-head trial [it won’t change my practice]. The answer for me is no for the real-world data.

AILAWADHI: I think that’s fair, and I keep that in mind, as well, as there have been multiple studies showing that the patient population that goes on to the prospective clinical trials is very different from the true patient population that you and I see in our clinics routinely.

I think we’ve also touched upon the pros and cons of VRd and DRd. I should point out that both are FDA approved. Whether we use one versus the other is [no] different. I still feel that there is a significant benefit of a PI/IMiD combination because we have seen that happen in the younger patients, so there is no reason to believe that in the transplant-ineligible population it would be different. Now, whether daratumumab/lenalidomide is equivalent or superior, I agree that unless there is a prospective head-to-head trial showing that, it’s hard to take that or just run with these kinds of data.

AILAWADHI: It seems that the intolerance or toxicity and patient preference [are the most common reasons]. Both are reasonable, and in some way, I feel that the financial aspect may also get rolled into patient preference because sometimes it’s very burdensome.

AILAWADHI: We touched upon what the maintenance therapy approach was, and it seemed that, at least in this population, Revlimid [appears] to be the most appropriate or most commonly used single-agent maintenance therapy. How do you determine which therapies to use in maintenance setting? We did talk about that, even though DRd from MAIA [NCT02252172] is continued that way,² but, Dr Nair, you’ve mentioned that typically you would drop the daratumumab and give them the single-agent maintenance for Revlimid. I would ask though, how long do you typically feel the maintenance therapy [should be] continued? Or is it [continuously] until progression?

NAIR: The goal post keeps [moving]. When we started, It was 2 years, then 3 years, and now it’s become indefinite until such time that there is disease progression or intolerance or some other [adverse] effect or complication. At this juncture, what we’ve been doing is just keeping [patients] on maintenance as long as we can.

SHARMA: Right now, I think we’re doing it also. In the practice, everybody that I know of [is doing the same]. It’s a long-term maintenance rather than cutting off at 2 or 3 years.

AILAWADHI: There’s someone who has said they’re [extremely] unlikely to use subcutaneous daratumumab. I’m assuming the qualifier is in the frontline setting. I’m assuming this is in the frontline setting, and we did say that it was [based on] preference to use VRd lite, CyBorD, or VRd, either one of those.

AILAWADHI: Has anybody had any unfavorable experience with subcutaneous daratumumab? Any line of therapy, any patient population, young, old, frontline, or relapse? Anybody who’s still using intravenous daratumumab in any setting?

SAWHNEY: I’m using only intravenous daratumumab. Cost recovery for subcutaneous is terrible. It’s really a logistics issue.

AILAWADHI: Fair enough. I would assume that’s where the practice setting does make a big difference. The way we look at it, having that chair open and turning over the subcutaneous injection versus the intravenous, that’s a huge consideration, but I can imagine where cost recovery would be very different from a reimbursement.

SAWHNEY: In a hospital or a 340B [Drug Pricing Program] practice, you will give everybody subcutaneous, but if you are a private practice, where cost recovery is a major issue, then it’s very hard to justify subcutaneous Rituxan [rituximab] or subcutaneous daratumumab [Darzalex Faspro]. It’s all about cost recovery.

_References:

_{1. Durie BGM, Kumar SK, Usmani SZ, et al. Daratumumab‐lenalidomide‐dexamethasone vs standard‐of‐care regimens: efficacy in transplant‐ineligible untreated myeloma. Am J Hematol. 2020;95(12):1486-1494. doi:10.1002/ajh.25963}

_{2. Facon T, Kumar S, Plesner T, et al; MAIA Trial Investigators. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249}

_{3. NCCN Clinical Practice Guidelines in Oncology. Multiple myeloma, version 6.2021. April 12, 2021. Accessed April 18, 2021. https://bit.ly/3sYjcQ9}