Progress and change in the management of multiple myeloma (MM)

DR LOVE: Welcome to “Oncology Nursing Update: Optimizing the Care of Patients with Newly Diagnosed Multiple Myeloma.” This is medical oncologist Dr Neil Love. For this program, I met with nurse practitioner Ms Charise Gleason from Emory Healthcare in Atlanta. To begin our discussion, I asked her to reflect on how the care of patients with multiple myeloma has evolved during her career.

MS GLEASON: I was initially a hematology nurse. And so 26 years ago, we were admitting myeloma patients to give them VAD. And there weren't a lot of options. It was VAD and then they went to transplant. I became a nurse practitioner in 2003 and that's really as new treatments started to develop at that time. But at that point we were talking to patients about a 3- to 5-year life expectancy. And so we don't even have that conversation any longer because with our newer drugs, and especially for a standard risk patient, their life expectancy is so long. And we're seeing patients in our practice that are 20 years out, 25 years out. So it looks very different. And the shift from the hospital to the ambulatory clinic and infusion center really is where the majority of your treatments are.

DR LOVE: Historically, up to a quarter of our audience has been in oncology less than 5 years. So they really don't have that perspective. The other thing I think was, I feel like people kind of were sicker, were having more morbidity from the disease, more bone problems 20 years ago. Was that the case?

MS GLEASON: It totally was the case. And you would also see that at relapse, where with bone agents now, we get those started right at diagnosis along with induction therapy. And throughout the course of their myeloma, when they relapse, you'll restart them again. So you don't see as many bone fractures. You might still see them at diagnosis, but not as many in that relapsed setting.

DR LOVE: Of course, working at Emory, particularly with Sagar Lonial, who's a medical oncologist who's been a real leader in the field we've been working with him more than 15 years, you were part really initially in trials of the real revolution that occurred, I guess, in the early 2000s, with novel agents. In particular, the regimen that everybody kind of came to and ended up using pretty quickly, which is RVd. And of course, Sagar and Emory were a big part of that, as a number of other places. Do you remember how things evolved when RVd got introduced and what you were seeing as you started to treat people with that? And maybe explain a little bit about what it is.

MS GLEASON: Yeah. We initially used bortezomib and then lenalidomide separately on clinical trials. But with early data, when you started combining treatment, we went to that RVd regimen early. And so that's lenalidomide, which is oral, bortezomib, which at the time was IV and now is subcutaneous, and then dexamethasone. And that triplet really changed things in the landscape for myeloma patients. And we started at a time when people were still giving single agent or doublets at that point. And patients would come in twice weekly for bortezomib. The lenalidomide was days 1 through 14. And then dexamethasone was a twice weekly dose at that point. And so you really had to monitor patients. Get them through the first cycle, I would think, was the most challenging at that point. It was just different. But the dexamethasone dosing was different as well. It got us away from that 40 mg, 4 days on, 4 days off, which patients didn't like, but still a lot of dexamethasone. A lot of centers now give the bortezomib weekly. We're still a center that will start it off twice weekly, but watching neuropathy closely and knowing that we can go down to weekly on that. So it's been a really good regimen and really changed the lives of myeloma patients.

DR LOVE: So before we go on, maybe just because proteasome inhibitors like bortezomib and IMiDs, specifically lenalidomide, we have some new CELMoDs coming along, are still a big part of treatment. Anything you want to say about particularly the tolerability issues that you see with these 2 types of agents and particularly bortezomib and lenalidomide?

MS GLEASON: Lenalidomide I think is very well tolerated. It does cause fatigue. It's myelosuppressive. So you do give the patients a week off to allow their counts to come back. Bortezomib it's really neuropathy that you're monitoring for. And so in the early days when we gave it IV, we learned quickly that it could cause very painful neuropathy for our patients. It's much better now because they receive it subcutaneous, but you still have to watch. And even if you're not seeing neuropathy, if, for instance, they're going through transplant so that stem cell collection and then transplant, a lot of times that's when that neuropathy can really kick in at that time. So it's still something we have to be very careful with, but it's a really good combination and patients tolerate it very well.

Patient- and disease-specific factors guiding therapeutic decision-making for newly diagnosed MM

DR LOVE: So we were kind of reminiscing back to being at the ONS Congress where you've joined us in the past. We were in Denver this year. We did 11 programs. And there, when we are doing all these things at once, we maybe do 3 programs in a day on different tumors. And we had a lot of people going to this, to multiple programs that we would refer back to other programs. And I was just thinking about one of the themes that in oncology in general that we always got into and will continue to get into, it's really a huge issue in oncology is first-line systemic treatment of patients with, I'm going to say widespread disease. Because in solid tumors, that generally means metastatic disease opposed to locally where you can treat localized. But in a lot of hematologic cancers, like the lymphomas and myeloma, it's just assumed to be systemic. And so they're getting the same thing, first-line therapy for widespread disease. And how, when you look across oncology in terms of that, how it's again globally how it's changed. And one of the things we always talk about almost every single program we do at ONS, and we did this year, is how now clinical biomarkers are entering into the treatment of patients in general, including myeloma, for example, and breast cancer, what kind of treatment you're going to get, depending upon your estrogen receptor status, your HER2 status, many other things, colon cancer, your KRAS status. So measurements of different types of assays of the tumor itself, so the treatment can be individualized. And every one of these cancers has their own sort of thing, so we see all different kinds of approaches. Urothelial, we see antibody-drug conjugates now in solid tumors and hematologic cancers being used first line. Breast cancer, there was just a big presentation at ASCO on that.

Diffuse large B-cell lymphoma. We have an antibody-drug conjugate with chemotherapy. So each one has their own flavor. But I guess a couple things about myelomas have always been different. And one is that they have this kind of, I mean, I'm just saying from my point of view, because we teach all parts of oncology, a very different approach to the younger patient than the older patient. And it really revolves around the use of one of the older, you already referred to it, that was happening when you first started, treatments, which is high-dose chemotherapy with autologous stem cell rescue, which continues to be used in patients who are able to tolerate it. And then with patients who either have comorbidities or they're older with comorbidities, they go down sort of another route. And it kind of seems like that continues to the present time. And really the big issue is whether they're going to get transplanted. After transplant, people usually get some kind of maintenance therapy, maybe indefinitely, like lenalidomide, for example. But any thoughts about how you think, you know that you have a patient who's got active myeloma that you and your team are going to be looking at in clinic that day. What are some of the things that you're thinking about as a regard, what are some of the individual characteristics of the patient, the patient's tumor, and their functional status that are going to kind of lead you in certain directions of treatment?

MS GLEASON: No, that's a good question. And this is with newer treatments what's changed for us. So the first thing you're going to look at with a new patient is are they transplant eligible or not? And that's going to take you down the road of the treatment selection. Though having said that, what we do know about those patients who aren't going to go to transplant, they still do well with the multi-drug regimen. So you just give them less of a dose or a little modified on that. And in the other pieces, we risk stratify based on high-risk, standard-risk disease. So you're looking at those abnormal cytogenetics, those FISH abnormalities that really helps guide us on our treatment. So knowing that, we're going to give, a transplant eligible patient is going to get a 4-drug regimen. Whether you're standard risk or high risk, you're transplant ineligible, we're still going to treat that same. We're going to give them the, a drug, a multi-drug regimen, just a little gentler. And then where that risk stratification really comes in is in that maintenance setting. So your patient who's not going to transplant, they're going to continue on their treatment. And depending on the risk factors associated with it, whether you can stop 1 or 2 of the drugs and go to a single agent maintenance later on or not, is really going to make that decision at that point.

DR LOVE: And it is very standard to look at these patients with myeloma to see particularly looking for 17p deletion and p53 status as the highest risk. But, of course, there are others in terms of the plan there. Another thing that's kind of come along that I think people hear a lot about, and particularly in trial, clinical trials, and in research centers like yours, and more and more I'm hearing this in the community, sort of a concept that has evolved over the last few years is what's called minimal residual disease. So an assay that'll kind of go subclinical, almost kind of like a tumor marker in a way, to detect the evidence of myeloma at very, very low levels. And when they're "MRD-negative" much different prognosis. Any thoughts about how that's affected taking care of patients in this first-line situation and how patients respond when they start seeing these MRD assays?

MS GLEASON: Yeah, this is why we do 4 drugs up front, right, for a transplant-eligible patient, because we know that if you give them that anti-CD38 antibody, so daratumumab or isatuximab, we know that we drive a deeper response. In the old days, like we were talking about, we used to hang back on drugs. We didn't want to give everything up-front because you needed it for some day. That's not the case anymore. You want to give our patients the benefit of the best treatment up front because you want to drive that response down deeper into the microenvironment. So when you're looking at minimal residual disease, you're looking at one in a million cells, which is pretty amazing. We didn't have that technology before. We're looking at a bone marrow biopsy. And so patients now, we're still looking at the same things we used to look at, but now we get that MRD looking at it after they've had induction therapy and then whether or not they go to transplant, then we have that period of time that we look at it afterwards as well and then annually on those patients. And it really tells us about the depth of their response. I think there's a lot more to learn from it. We still don't have a consensus on how we use it. But everybody in the myeloma community seems to agree. Now it's very important in how we look at our patients' response to therapy.

Role of anti-CD38 antibodies in the management of MM

DR LOVE: It's funny when I sit down and chat with people, I always, sometimes I get these little flashes of memory and I don't know where they — of things I haven't thought about for years. And as you were just talking about MRD, I remember the first time I worked with your partner there, Sagar. And at that time, he had pulled this picture of an iceberg out. And he would show it. I knew you would remember it, because that was the first time really I started to really think about what eventually became MRD, because he would show this picture and see how much ice was really under the water. And that's really the whole issue of subclinical disease. You mentioned the other, the next big step that occurred in up-front treatment of myeloma was the evolution of anti-CD38 antibodies that you just talked about, daratumumab and isatuximab. Can you talk a little bit about your vision and how you explain to patients what these antibodies are, why they're effective, and how it gets integrated? And it's also used in relapsed disease, but now more and more as a standard up front. What do you say to patients about what these are and how much they add? To me, it was really one of the major steps forward in the field.

MS GLEASON: Yeah, I agree. I think, myself as a nurse practitioner, and then our nursing team reinforces the education on this. We talk about the synergy that you get with these drugs. There's a reason we pair drugs together. And the difference in that monoclonal antibody that really attaches to that plasma cell in a different way, it's the multiple ways that we cause cell death in that myeloma cell. It's very well tolerated for patients. As a matter of fact, patients are very sad when they have to come off of it due to progression. But especially since we tend to use daratumumab more, and we participated in the clinical trials, both monotherapy and in combination. And when we went to subcutaneous, it's just so well tolerated. And really very few side effects. Patients do well with it.

DR LOVE: So yeah, that really was a huge moment in myeloma. And, of course, and again, we always talk about this in ONS, that particularly in the up-front setting where there are a lot of patients, people look to what's called Phase III trials to where they compare the standard of care versus the experimental. And there are a whole bunch of trials using, often it was RVd, because, I mean, that really became, or some variation of that to that same therapy, or might have been RD, but whatever, novel therapy plus or without anti-CD38. And they immediately started to see huge benefits without a whole lot of serious toxicity. Some things that we'll talk about. But I think one of the things that was really interesting, again thinking about all across oncology. I don't think there was a meeting we did this year, of the 11 we did at ONS, where we didn't get into the issue of having multiple similarly acting agents within the same treatment class. It happens all the — there are different proteasome inhibitors. There's carfilzomib, for example. In breast cancer, the classic example was letrozole and anastrozole. Nobody could tell — they never were compared, but they looked identical. And there are all kinds of variations. Again, in breast cancer 3 CDK inhibitors to choose from, and on and on. EGFR, lung cancer, et cetera. But I can't think of another situation where you had — many times in oncology, you'll see trials indirectly, they seem to have similar benefit. I mean, you're not comparing them directly, but they're both compared against the same thing. They reduce the chance of recurrence by maybe 50% or whatever it might be. And then you try to figure out which one are you going to give, maybe there's a little bit difference in the toxicity, so hard to decide often. But the thing that happened in myeloma that was so interesting was that one of them, you have these 2 drugs, that if you actually look at the trials, I mean, I think it was very difficult to separate either the efficacy or tolerability. I mean, maybe there is, but I've never really heard anybody say that. But the thing that was interesting was that one got a subQ formulation before the other one did, which is daratumumab. And of course, everybody flipped over to that because that's so much more patient friendly. And you can talk about the difference between what you saw when it switched to subQ. And so really, I think now we're in a situation where almost every patient's getting an anti-CD38 antibody up-front. What you pair it with, maybe that varies a little bit, but it's pretty standard, younger, older. But you have the option of subQ. But now, as of the ASCO meeting that just happened, it looks like there's going to be subQ for isatuximab. And it actually is going to be a little bit different. It's going to be an on-body device instead of having to be given by infusion. I don't even know. Have you ever used that incidentally? I rarely find people who've even tried it.

MS GLEASON: The on-body device?

DR LOVE: Yeah.

MS GLEASON: No, I've not. But I've seen it. And I've been in some talks where they've presented that. So that's going to be interesting.

DR LOVE: Right.

MS GLEASON: The thing with subcutaneous for patients, cancer, whatever type of cancer you have, patients want to gain some control back, right? They don't want to spend a lot of time in the infusion center. The more time they have doing what they want to do, the better. And so the subcutaneous formulations really help patients not have to spend as much time in that infusion chair so they can come in, they can get their treatment, and they can go. And I think it being very well tolerated is just, it makes it so much easier for a patient.

DR LOVE: Yeah, and, I mean, again, not too many situations right now. We're starting to see the immune checkpoint inhibitors starting to become subQ. It'll be interesting to see how that affects what people do. And it seemed like, particularly, specifically with daratumumab there was a lot less toxicity. The infusion was, well, the time and the infusion, sometimes the first one was very long, because they had toxicity. So it seemed like the patient experience was clearly better subQ. And it'll be interesting to see when this on-body thing comes on. I've talked to at least some docs who've used it in trial, who think the nurses like it a lot. They think maybe it could someday maybe be self-administered. I don't know whether that's feasible or not. But it's just so interesting how these different factors affect what treatment is. Because you've been seeing great data with both of them. I don't know. It's hard to separate out. They have one that's a great trial and everybody talks about it, and another one talks. But I mean, is that at your center, of course, you're one of the top centers in the world on myeloma, do you think the perception is that these are 2 essentially identical, but right now the difference is the subQ?

MS GLEASON: I think so. I think they're very similar. We used both on clinical trials. It's just daratumumab was approved first and then subcutaneous. So we just tend to use more of that at our center. But the data is really good for both of them.

DR LOVE: And what do you say to a patient who's about to begin either one of these agents in terms of tolerability issues that might come up or complications? And what have you actually observed?

MS GLEASON: Yeah, so with the subcutaneous, we tell them there's a very low chance of having a reaction at that first dose. So that one we do give pre-meds. After that, we don't need to. We talk about maybe some local site discomfort or they can get some redness around it or some itching at that site. We talk about, especially because it's in combination, so those other side effects because of the combination drugs, when to reach out to us, the potential for infection issues, they're on prophylaxis drugs for an antiviral, if they're on the, with an IMiD, they're on prophylaxis for DVT or PE. So all those, you put all those things in place. It isn't just the myeloma drugs. It's the other things for prophylaxis. So you have patients that go from not taking much of anything to a lot of things now. So it's an adjustment for them. But you really try to tease out in the regimen which side effect they're getting. You don't dose reduce daratumumab, for instance. It's the dose that it is. And that's not usually the culprit when they're having side effects. It's other drugs like dexamethasone that you typically have to adjust. But it's getting them typically through the first cycle. And then they do really well after that. And I think it really helps too, they tend to see results quickly, right? And so when you can see that you're responding to your treatment, that really helps as well.

DR LOVE: When you have patients who do go for transplant, how do you see them? Usually, again, they're usually better condition, although I'm curious what the oldest patient is that you've transplanted there. But how do they, how are they when they get back from transplant?

MS GLEASON: It's a mix. I think the oldest patient, one of our colleagues probably transplants patients, Dr Nooka, that's, that are a little bit older. But I think for Dr Lonial and I, I think the oldest patient was probably 81. They tend to be younger. But you really look at their performance status. It's not so much their age. Many patients do quite well with transplant, more fatigue. And some people get a little more, take more of a hit after it. That's a big dose of melphalan. If you're going to adjust anything on somebody that's an older patient that's still going to transplant, for instance, you might do a dose reduce of melphalan. So it's that alkylating agent. But for the most part, patients bounce back pretty quickly. They tend to need a little more sleep than they used to and a little more fatigue. But by 6 months, most people are back to their normal routine. And a lot of patients, it's even sooner, especially a younger patient. And a lot of patients want to go back to work and get back to their activities earlier. So we look for, we do our first restaging for a standard-risk patient after transplant around day 100. And for a high-risk patient, we do that at day 60. So we can get that maintenance started at that time.

Emerging treatment options for smoldering myeloma

DR LOVE: So just another issue, just to sort of mention that kind of interesting in terms of up-front treatment, which is the issue of smoldering myeloma. And in particular, high-risk smoldering myeloma. And again, your center has been very instrumental in researching this. Can you explain a little bit about what smoldering myeloma is? What high-risk smoldering is? And now the evolution again of anti-CD38, particularly daratumumab being used in these patients, which kind of surprised me. I think it was a fairly recent trial. They saw great benefits treating these people who always used to be observed.

MS GLEASON: That's true. Yes, so smoldering is, they've got a higher protein than somebody with monoclonal gammopathy of unknown significance. So they come in with a little bit more disease burden, but then we further risk stratify. Are they high risk? Do they have a higher free light chain, for instance, that puts them in that higher-risk category? And those are the only patients that you would consider treating at this point. And it is in the context of a clinical trial. And so we've had multiple trials and we have used, we also had the daratumumab clinical trial, where they got it for a period of time and then there was a maintenance phase afterwards on that. We've also used lenalidomide on trial, on the ECOG trial. And right now, then we're also using iberdomide, which is one of the newer drugs that we're looking at, but still very well tolerated. And the thought behind that is, can you give a defined number of cycles of treatment to try to keep these patients from converting to symptomatic myeloma so they never have those organ-related side effects that would force us then to be more aggressive with their treatment? And so I think we've learned a lot from that and the benefit in that 2-year period. So most of your clinical trials now for high-risk smoldering are with a treatment for around that 2-year period of time. And that's based on the data that came out from the ECOG trial.

DR LOVE: I'm curious if you actually plan to use it or have used it?

MS GLEASON: We're still using it for clinical trials, honestly. I think everybody hasn't agreed in our practice on that.

We have not started giving it in the high-risk smoldering.

DR LOVE: That's interesting.

MS GLEASON: At our center, yet.

Optimizing long-term outcomes for patients with MM

DR LOVE: So another thing I'm kind of curious about is I'm sure one of the things patients who are about to start treatment first line for myeloma, one of the things that's most on their mind, of course, is what to expect from the future and particularly how long they might live. Although in a way, it's kind of interesting because again, flashing back to Dr Lonial, I can remember cases he would tell me about over the years of people who went from one trial to the other trial to the — they kept going on the newest treatment before it ever got used. So it's kind of hard to predict, right now, maybe they have a prognosis of X, but maybe by the time you get to X, there's going to be some agents out there, which actually is, it seems to be occurring. And we'll talk a little bit about that. But right now, given what we know in terms of the follow-up, 2 patients who've gotten what usually is anti-CD38 plus either RVd or some, some variation of that, roughly what are you expecting in terms of their overall survival, if they're standard risk or if they're this high, much smaller group that's very high risk in terms of their kind of average or median survival?

MS GLEASON: Yeah, a standard risk patient for some of those patients, they may have their up-front therapy, go to transplant and go on lenalidomide maintenance, and they may never progress again. I mean, we see that. The difference is it's hard to predict which patients because they're standard risk. We know with high-risk patients, we have to be more aggressive, but we don't really give patients times. We expect patients to live a very long time with their disease and it to be more of a chronic disease that they're taking a medication for. I think the difference is they're almost always on medication now. Years ago, you would give them a treatment and then they would be off of treatment. And then they would progress and you would go to a treatment again. And that's just not the case now. It's a myeloma world of continuous therapy.

DR LOVE: And again, we've spent entire programs on this series, for example, on one of the most exciting developments in oncology in general, bispecific antibodies and CAR-T therapy and other therapies, all these newer approaches that I think are going to, just like it always happens in oncology, you find a drug that works in people who have relapsed disease, they're going to start studying it. So in up-front, so now we've got trials looking at all the things I just talked about up front, instead of going to transplant, going to CAR-T, going to transplant and CAR-T. So who knows what's going to happen, 5 or 10 years from now, but I guess let's just put it this way. It's not unusual to see somebody survive 10 years or more. Is that a reasonable thought?

MS GLEASON: I think that's totally reasonable. Yes. I think a lot of myeloma patients, if you look at the median age of diagnosis, in a practice like ours, we see all ages, but the median age is later in life. So in the 60s. So a lot of patients will die from something other than their myeloma because our treatments are just so good. But you're right. We move those treatments. We start them in that relapsed refractory patient population. And then as we use them more, we start moving them up-front. And that's exactly what we're doing with bispecific antibodies and CAR-T therapies. So CAR-T is already approved for first relapse. But we're looking at it in the up-front setting on clinical trials as well. And bispecifics are off the shelf, easy to use. And we're also looking at the combination of bispecifics. So 2 different targets. And how do we use those? So it's pretty exciting.

DR LOVE: For sure. I was just reflecting back to though on this issue of first-line therapy and widespread disease across oncology. And like the scenario you just described in a disease that looked a lot like maybe pancreatic cancer 20 years ago, but unfortunately in pancreatic the discussion is not that much different than it was 15 or 20 years ago. But then there are pockets of oncology where you're seeing explosions. Myeloma certainly is one of those.

Tailoring therapy for older adults and patients with preexisting comorbidities

DR LOVE: I want to get into your cases a little bit so we can sort of get into this issue that we always get into at ONS meetings, which is when we start getting into, the reason we always talk about real patients is the theme of why was it different to take care of this patient than another patient in the same oncologic situation but a different person? So different comorbidities, age, attitude, social support, you name it. All the things that, beyond just the tumor. Before we kind of see how that plays out in some of your patients, just kind of curious in general, what are some of the things, again, that you're thinking to look at in a patient you know you're going to be seeing with first-line therapy? And also, how you look at patients, let's say, myeloma has always been a great leader looking at older patients. You guys came up with the idea of very elderly, which I never heard before. But, and how that, how this thought process in your mind differs when you have a 70-year-old patient coming in compared to an 88-year-old?

MS GLEASON: Yeah, so you're still going to look at their performance status. You're going to look at their other comorbidities and those side effects that they have from those things. So you're risk stratifying, but you're also looking at the patient in front of you. You're looking at the care system they have. Do they have a care partner? What is that social system like available for them? And so you look at that for these patients and you could have a 50-year-old patient that comes in that just doesn't have the things in place, for instance, to take them to a transplant. So you really need to look at the whole picture of the person who's in front of you. And so if I'm thinking about an older patient who we know is not a transplant candidate, there are really good treatment options for them. And as we said before, you're still going to give them the benefit of a multi-drug regimen, you're just going to do it in a lighter fashion.

DR LOVE: So one other sort of generic issue about first-line therapy that I hear a lot from oncologists, and you kind of referred to it before earlier, is the issue of the corticosteroids that these patients end up receiving. And I think in a way, again, when I think across oncology and I think about steroids, the first place I think about is you guys. And you talked about the dosing, et cetera. And also particularly the issue of dosing in the very elderly. I'm curious what kind of issues do you think about with people getting steroids? The hyper syndrome that they may get, not being able to sleep, diabetic issues? What you see and how you kind of adjust dosing to that?

MS GLEASON: Definitely. And they might have that history of diabetes, right? So you want to dose steroids very carefully. They don't tolerate the higher doses. And while you do get that synergy, and we know that dexamethasone works well in our regimens, we definitely go to a lower dose version. It also makes them more at risk for infections. And so these are things that we have to monitor throughout. So we might still hit it with a little bit higher of a dose of steroid in cycle 1, still nothing like we would do for a younger patient, just to get that response. But watching carefully and listening to their side effects and dialing it down quickly and then eventually stopping it. You don't have to keep steroids going for the whole time that they're on their therapy.

DR LOVE: One other sort of general thing I was going to ask you about in terms of, again, initial treatment, even longer-term treatment. You talked about the issue of preventive anti-infectives. What about the issue of vaccinations? Do people with myeloma have normal responses to vaccinations?

MS GLEASON: They don't. And we did a lot of that work during COVID, looking at how are our patients responding to COVID vaccines. And our personal experience, what we learned is those patients that had good disease control that were on a single-agent, something like lenalidomide, those are the patients who mounted a response to vaccines. So we know that that's an issue in our patients. So we still have them get a flu vaccine. We still make sure they're caught up on meningococcal. But we know that that response isn't going to be as good for them. So we want to make sure that those around them are vaccinated.

Case: A woman in her early 80s with newly diagnosed transplant-ineligible MM who experienced a complete response with first-line daratumumab/lenalidomide and low-dose dexamethasone

DR LOVE: Alright, let's get into your cases, beginning with this 80-year-old woman. When did you first see her?

MS GLEASON: This was about 3 years ago at that time. So, she came in, increased fatigue, some pain and was anemic. And that's really the thing that drove her primary care provider to take another look because it's not uncommon to be a little more fatigued at that age. And she was anemic. And they had an abnormal protein. She didn't actually, even though she had some back pain, she didn't actually have lytic lesions, which is a little bit different, right? We think of everybody coming in having that bone disease. Her bone marrow was pretty full of disease. And she just was a little bit frail. She had that history of A-fib and was already on apixaban, some hypertension that was well controlled. But she already had a baseline neuropathy, too. So we really had to think about that for this particular patient, knowing that some of our treatments have that potential to cause neuropathy. So it's really looking at that patient and tailoring that treatment and knowing that this is going to have to be monitored closely. And I think that's the thing that we count on our infusion nurses to help us with as well, right? We see them at the start of a cycle. They go to the infusion center to get their treatment. So the nurses really play a big role in that.

DR LOVE: What was her neuropathy from? Did she have diabetes?

MS GLEASON: She did have some diabetes. So it was well controlled. But we have patients that come in that will have a baseline neuropathy for different reasons. And so it's just something that you have to keep in mind when you're treating them. So a patient like this who's not transplant eligible, and she wasn't, you still want to give her that benefit of a good regimen. And so we tend to go to a regimen with daratumumab/lenalidomide and low-dose dexamethasone, leaving off the proteasome inhibitor, which was consistent with how the MAIA trial did it. And she responded beautifully to this. She tolerated it well. We did a lower dose of lenalidomide for her. She started at still a pretty decent dex dose at 20 mg, but then we reduced that as well. But she responded well, went into a complete response and MRD negative, which is the best case that you could get for the patient.

DR LOVE: So you mentioned here that the study really led to the treatment she got. The median progression-free survival is 64 months. That's more than 5 years. So if these older patients are getting this regimen without a proteasome inhibitor, and of course now they haven't even got second-line therapy, but they get to, on average, they get to 5 years just from the first treatment really makes your point about 10 years and more being a reasonable goal for a lot of these patients. And now — I'm curious, too, what this woman's lifestyle is like. Does she have a family? What does she like to do? What's her quality of life?

MS GLEASON: Yeah, she actually moved to the Atlanta area to be near her daughter. And she was still very active. She would bring her knitting with her to clinic. And she had grandchildren in town and she tolerated treatment. She came, got her treatment. It gets to once a month with daratumumab. And so sees us briefly and then gets treatment and is living her life.

DR LOVE: What kind of work did she do in the past? And what was her attitude about information? Was she asking a lot of questions, looking things up, or just asking you what to do?

MS GLEASON: No. I find that myeloma patients ask a lot of questions. And that's good, right? They're pretty educated. She was a retired schoolteacher. And so, she was used to information, right, and wanting information. And she's an active member of the local support group.

DR LOVE: Really?

MS GLEASON: Yes. So yeah, and still does that.

DR LOVE: Yeah, it's interesting. It's kind of, in a way, now with all our electronic abilities to communicate like we are right now, you kind of maybe don't necessarily think about these live — I mean, I don't know, maybe these support groups are Zoom, too, for all I know. But what do you think people get out of — what do you think they get out of the support groups? I mean, I guess the obvious would be support and encouragement. But any specific things that you think they get out of that?

MS GLEASON: I think there's a psychosocial support that they get in hearing somebody else's case or seeing somebody that's doing really well. Now, we do get a lot of questions because it'll be like, well, so-and-so's on this treatment, why is my treatment different? And you have that conversation that everybody's different and how you get treated. But they do Zoom as well since COVID. So they do a little bit of a hybrid there. But I think they become friends with each other. And they have sessions that focus on the caregivers, for instance. And I think that's nice for the families as well.

DR LOVE: It's great that this lady is doing so well. Just out of curiosity, if she were to have disease progression at some point, I guess one of the things you would think probably she's not going to be a candidate for CAR-T, although I would ask if that would be a possibility because I know there are people who are not eligible for transplant that could go to CAR-T. But really, in particular, do you think she would be a candidate for a bispecific? Because that seems to be much more tolerable. Seems like somebody like that could probably handle it. What do you think?

MS GLEASON: I think so. We have taken patients as 82, 83 to CAR-T, but it really depends on their cardiac status too. That particular patient had A-fib and a little bit older now. So probably would think about a bispecific.

DR LOVE: So I was mentioning, I kept hearing about cases from Sagar of patients going from trial to trial. I got to tell you that we did the — I've been doing patient interviews ever since the pandemic really. And one of my favorite examples of that was, I did a video with a patient, a man who'd been on the bispecific teclistamab, which, of course, is one of the bispecifics out there. He'd been on it for a year and a half, very smooth, almost no toxicity, complete remission, doing great. And the day that I interviewed him was the day it was approved.

MS GLEASON: That's great.

DR LOVE: So he had been on it for a year and a half before it got out and he'd been enjoying the benefit of it. And again, I keep thinking of all your patients I've heard about through Sagar with just that same story. They went to one trial, then they go to something else, and then they like, their history is the history of the evolution of treatment. But just a different story nowadays with trials, the real opportunity, not just to help future patients, but current ones.

Case: A man in his early 60s with progressive back pain from standard-risk MM who experienced a complete response with daratumumab with lenalidomide/bortezomib/dexamethasone

DR LOVE: Alright, well, now we have a much younger patient, 62-year-old. Now we're getting into the arena of transplant eligibility. I don't know whether this patient was or not, but 62, that would be one thing I'd be thinking about if he was going to be showing up in clinic. But what happened with him?

MS GLEASON: Absolutely. So he came in. He did have a lot of bone disease. So it was progressive back pain. And on workup, he had a lot of compression fractures. So he's somebody, he was a little bit hypercalcemic as well with that and significant pain issues at that point. So he had a kyphoplasty. He was standard-risk disease though. We did induction with dara-RVd for him, did 4 cycles, did stem cell collection and took him to transplant. And he achieved a complete CR, serum CR, MRD-negative and just is on single-agent lenalidomide maintenance now. And it took us a while to get him through the pain issues with help from, other colleagues, orthopedics and that. But he's off of all pain medicine now and pretty much back to his normal life. The last time I saw him, he had just come back from 2 European trips and then was going to Alaska. So, I mean, he's traveling, he feels great and he's doing really well. And he had some residual neuropathy after transplant. So we delayed starting his lenalidomide just a little bit, but he's on it and doing well.

DR LOVE: So it's natural when we ask people to present cases, we often hear success stories. And I guess it's important to say that not every patient does as well as the 2 people you presented here, but a lot of them do. And I think the fact that this is not a very unusual story for either one of these patients is noteworthy. What kind of work has he done? Is he still working? Family? What's his life like?

MS GLEASON: Yeah, he's married. He has children that are out of state, grown children and grandchildren. He is working. He's in a distribution business and, yeah, so back to kind of self-employed, yeah, back to normal work, back to golfing, which with the back issues like he had, they, patients don't always get back to some of their prior activities. So, but it took him a little bit of time to get there.

DR LOVE: So as you know, one of our themes over the years is when was the last time somebody said to you, why are you in oncology? Isn't it depressing? And I love hearing what people have to say about that, particularly people just entering the field. But these 2 cases again are really good examples and certainly, I know you and everybody sees situations that are very, very difficult. But you also see situations where people really go through transformation and not just becoming treated well for their disease or even cured, but maybe even transformed at a deeper level. Here you have a young man, 62 years old, presents with what I would call disseminated cancer, right? And not like it's like a single lesion we can take out. And he's in severe pain. I can imagine his mental state once he got the diagnosis. I'm curious what you've seen in him and other patients when they go through things they never thought they could get through, how it affects them and also how it affects you to see that?

MS GLEASON: I think this one was a little more challenging in how he felt because he just struggled with the, how this happened to me aspect, right? I was living my normal life, doing my normal business. I had some back pain and then bam, I'm in here and I've lost height in my spine and I've had kyphoplasties and then I'm told I have this cancer I've never heard of. And so I think, especially early on, we spend a lot of time helping support our patients through that. And you're right, the first 2 cases patients have done very well. We see all aspects of it. Not everybody does as well, though up-front they typically do a little bit better because our treatment regimens are better, but the high-risk patients still can be very challenging. But you get to know your patients and you see them so frequently. So you're part of getting them to where they need to be and getting them over this piece of it. And so I think that's where we come in and we just spend so much time with them. But I think for this gentleman, when he looks back to where he was 8 months ago, he can look and say, you're right, I am so much better. And I've, I'm now able to do these things again. And that is our goal for patients. There's a lot of work to do up-front to get you to a place that you can get back to what you feel like is normal activity for you. Even if you don't go back to what you consider a normal baseline.

Building therapeutic relationships and integrating holistic care in oncology practice

DR LOVE: And another theme that we've talked about over the years at ONS is what we call the bond that heals, which is the idea that the relationship that you have with a patient is a special benefit to them that goes beyond the treatment, the anti-tumor strategy you're using, that they value, that they benefit by the connection they have with you. Any thoughts about how that played out in, for example, these 2 patients and what you see? Do you feel that as you practice?

MS GLEASON: Yeah, I think that it's very important to have a connection with your patient. And I'm not the only advanced practice provider or nurse in our practice. And we try not to have patients see somebody different every time they come because having that connection with them is really important because we do a teamwork approach to taking care of our patients with our physicians. So Dr Lonial isn't able to see every patient all the time. And it's important for the patient to have a good relationship with the people that are taking care of them. And sometimes it's not a good fit and you've got to find that right fit because that's, they're depending on our expertise, they're depending on us to help manage their side effects and to give them the information, right? And it's just, it's an amazing relationship and we're very fortunate to do what we do. I think we're drawn to oncology for a reason. We all find our specialties, but it's a very special field to practice in.

DR LOVE: And again, another theme we've had over the years in oncology is thinking about, again, nurses who are new to oncology, who are trying to understand what's going on and seeing things that maybe they hadn't ever seen before in terms of patients suffering and families dealing with really difficult issues and the challenge of avoiding burnout and taking care of yourself, your own self-health. One of the things we've done at ONS a number of times is when we introduce the faculty, we have them show pictures of what they do to get away from work. Cause one of the advice we kept getting all the time was you got to get away from it. But I'm just sort of curious if you have any observations on burnout and any advice to people just starting the field.

MS GLEASON: Yeah, I think when you're starting out, you do also have to figure out those boundaries for yourself. You do have to take downtime, do those things that you enjoy, spend time with your family, if you like to travel, you still need to do all those things, and count on your team members to get you through. A lot of nursing and advanced practice have gone to residencies or fellowships to bring new people into oncology. And I think that's helpful as well to give them resources. But I think, especially at your bigger centers, we have a lot of resources available to us, people to talk to when you need to about your patients or somebody that didn't do well, we do still lose patients. So it's important, I think for those of us that are more experienced, too, to help mentor our new colleagues that have joined oncology.

DR LOVE: Did you say something about a fellowship?

MS GLEASON: Yeah, we have advanced practice fellowships. So for nurse practitioners and physician assistants they do like a 1-year oncology rotation through all the specialties. And our nurses have residency programs. So bringing new nurses into oncology and they rotate through the different specialties, so they're learning about all of oncology. And it's not something just we do, but I think that's more available throughout, especially at your academic centers. It's a really good way to bring new practitioners and nurses into oncology.

DR LOVE: One final issue I wanted to mention to you, and this came out a lot when I was talking to the patients with breast cancer, which is complementary strategies. Everything from nutrition to meditation, alternative, massage therapy, acupuncture, anything, and you mentioned kyphoplasty before, which of course is a little bit more medical. But what kind of advice do you — I'm sure people ask you, what should I eat? What do I do about exercise? Any specific strategies you think are helpful, particularly in myeloma?

MS GLEASON: Yeah, I think it's important for myeloma patients to move. They may not be able to exercise in a way that they used to, but movement's essential. If you can just get out and walk, it's so beneficial for you. I do refer a lot of patients for acupuncture, especially patients who have neuropathy. We're very fortunate at our center, we have an integrative oncology practice. So they specialize in acupuncture, in vitamins, those things that you can take, massage. Physical therapy for a lot of patients is very beneficial. And we have nutritionists as well. So yes, get a lot of questions about, can I eat this? Can I eat that? Or can I have a drink? Those kinds of things. And we tend to do things in moderation, but definitely we get the advice of our nutritionists as well with patients, especially if they're having issues or diarrhea related to lenalidomide, those kind of things. There's help.

DR LOVE: I was just sort of, again, flashing a little bit on Sagar. And one of the things I was kind of thinking about him is he has like a little bit more of a sense of humor than most oncologists. And I kind of, I was sort of wondering whether you do also, and where that kind of fits into your relationship in your clinic?

MS GLEASON: Yes, Well, we're close to the same age. I'm a little older than he is, but we both enjoy movies. And I think we have a similar sense of humor that's a little bit dry. Our younger colleagues in our clinic don't always get it. But yes, we bounce things off of each other. I think humor in what we do is very important as well. So yes, I think that's very helpful. And Sagar and I have worked well together for these years. And so it's been a good partnership.

DR LOVE: This concludes our program. Special thanks to Ms Gleason, and thank you for listening. This is Dr Neil Love for Oncology Nursing Update.