← The Fellow on Call: The Heme/Onc Podcast
The Fellow on Call: The Heme/Onc Podcast
Episode 149: Myeloma Series, Pt. 9 - Maintenance for Multiple Myeloma (2026)
Ronak Mistry, Vivek Patel, Dan Hausrath
Loading summary
Transcript48 lines
- [00:00]
A
Hey, friends. This episode of the Fellow on Call is not meant to be used for medical advice and is intended for educational purposes only. Patient information has been modified to ensure privacy. The views expressed in this episode do not necessarily reflect the views of our employers. Enjoy. Oncology isn't a solo practice with Primum. You can ask the questions you can't ask anywhere else, anonymously or not, and get answers in hours from world class oncologists. It's completely free. Try today at Premum Co. Welcome to another episode of the called the hemonk Podcast. We're coming at you from Merlot University Medical Center. I'm Ronuk.
- [00:38]
B
I'm Vivek.
- [00:39]
C
And I'm Sean.
- [00:40]
A
And in today's episode, we're continuing on our myeloma journey. This time we've made it to maintenance therapy. Guys.
- [00:46]
B
Yeah, myeloma is complicated. I know everybody slogged through this series. Sean loves this stuff. It makes my head hurt. Maintenance is another very challenging, evolving space. Really excited to talk about the data, to really talk about the data. And so that people aren't just doing things randomly, checking mrd, randomly doing things randomly. It's important to know what we have and where the field is heading. So really, really looking forward to getting into this.
- [01:08]
C
It can certainly be a little bit complicated, especially because of how quickly things are evolving. But I do think that one of the things I enjoy most about myeloma is that there's a lot of opportunities for patients where they have specific situations or based off of their own kind of personal preferences to tailor the care based off of them. So obviously we want to try to use whatever is the standard of care in most evidence based practices. But obviously that's not something that we can do for every single patient. There are circumstances that come up where we have to pivot. And so one of the things I enjoy about myeloma is that there's a lot of ways for us to help have those conversations with patients. And I think it's really important to understand the data and understand why we do certain things. That way when you're counseling patients, you can have that discussion with them and make sure that they're fully informed and understand exactly kind of what the pros and cons are to all the different approaches that we have.
- [01:56]
A
That sounds great. And I, and I love that perspective on our current therapies. So, guys, let's roll that show. All right, so we are here today to talk all about maintenance therapy for multiple myeloma. This just continues on our journey through this disease type and we've covered a lot of ground. You know something that continues to blow my mind whenever we talk about these, even in the last episode. Listeners, you may have noticed that we, when we quote these studies, we're talking about progression free survival and overall survival over like six, seven, eight years. I mean these patients are living longer thanks to the current therapies that we have. This is so different than all the other disease subtypes that we talk about where we're talking about months or maybe like a year. But really, really, really fascinating and so cool to be at a point in in time where we can have these conversations.
- [02:46]
B
Yeah, myeloma is interesting. Excited to get into this one really briefly. The only fun fact that we're gonna do for our banter today is that everybody needs to watch Bridgerton and Love is Blind. These are two of the best Netflix series that have ever been created. And if you haven't watched it yet, you're really missing out. These are two really good seasons. Highly recommend. 2026, Love is Blind Bridgerton. They really did it right. And so 10 out of 10 recommend.
- [03:10]
A
I'm excited for the day where we do our spinoff podcast just to talk about these shows. Yvette. Cause I'm so in on both of these right now.
- [03:18]
B
It will break down scene by scene. Everything that's happening I have not watched either.
- [03:21]
C
So I think I need to get caught up.
- [03:23]
A
Sean, we have to record this fast so you can get to work. Speaking of which, Vivek, let's roll right into that case so Sean can enjoy more fun things.
- [03:32]
B
All right, so we'll reference back to this 55 year old female we had in our transplant episode. Very healthy, newly diagnosed standard risk IgG Kappa multiple myeloma. Remember, it'll be in our show notes that IMWG new high risk criteria. It's important to just keep on looking that up so you familiarize yourself with those high risk cytogenic features. She didn't have any of those. She was treated with DARA VRD for four cycles per the Perseus trial and achieved a VGPR with a detectable M spike but not quantifiable in a normal free light chain ratio. She had a bone marrow biopsy that showed 5% population of plasma cells and she was ready to get her auto transplant. She got high dose mephalan followed by autologous stem cell rescue. Remember we talked about the data behind this in our last episode and, and sort of the nuances in the involving management with MRD testing after recovery. She was found to be in a CR and was started on DARA revlimid maintenance. The key thing for everybody to know now is that all patients should at least get revlimid maintenance post transplant and we continue that until progression. So before we get into the DARA revlimid data, because things get really complicated there, especially with these quad inductions, can one of you talk about where did we get to revlimid maintenance?
- [04:44]
C
So there were several studies that were done in the early 2000s, early 2000s that were looking at the role of single agent Lenalidomide as maintenance after induction for multiple myeloma. These trials were all done in different areas. So some are done in the us, some are done in Europe. There is actually a large meta analysis that combined three of these largest trials published by McCarthy et al in about 2017 in JCO. This meta analysis, I think is probably the most compelling evidence for why we do lenolidomide maintenance and myeloma. And so each of the original RCTs were only powered for progression free survival, and they did indeed all show improvement in progression free survival, while only the CALG B study, which was conducted in the US showed an overall survival benefit. However, when they looked at it in the meta analysis, we did see that there was an overall survival benefit with lenalidomide when all three of these trials were combined. So this was the CALG B trial in the US and Gemema trial in Italy and then an IFM trial that was conducted in France. The seven year overall survival with lenalidomide maintenance was 62% versus 50% in the non maintenance arms. Important to note though, there was also an increased risk of second primary malignancies, both hematologic and solid tumor malignancies in the patients that got lenalidomide maintenance. So for hematologic malignancies, things like leukemias, for example, There is a 6% rate in the lenolidomide group versus just 3% in the placebo group. Similarly for solid tumors, so things like skin cancers, for example, There was a 7% rate of second primary solid malignancy with lenalidomide maintenance versus just 4% in the placebo group.
- [06:25]
A
So from these studies, Sean, what you just mentioned is that clearly there's an overall survival benefit, but it does not come without its fair share of risks. And so really, if we're subjecting patients to therapy and to the side effects, we really do want to make sure that the overall survival benefit is there. So now that we have quadruplet inductions, are we now introducing anti CD38 in addition to revlimid in maintenance. How are we doing this in the current landscape?
- [06:52]
B
I'll walk through some of the data and I'll kick it back to you guys to walk through some of the other trials. That way it's not just me talking the whole time. The short answer I do have to say is that we really don't know. And some of these quad trials just said, hey, just give continue on DARA in maintenance and we'll talk about the nuances of that and how MrD might influence that. So I'm gonna start off by talking about the Cassiopeia trial. So this was one of the early quad versus triplet trials run in Europe and it randomized patients to Daratumumab plus velcade, thalidomide, dexamethasone. So DARA VTD versus vtd. You listeners are probably like thalidomide, what about revlimid, you know, what about lenalidomide? And you know, in Europe, for cost effective reasons, thalidomide was commonly used. So that's where this came from. So it was DARA VTD versus vtd, similar to kind of how perseus was DARA VRD versus vrd. These patients underwent a second randomization for maintenance and this was daratumumab versus placebo, which to me is insane. We knew that there was an overall survival benefit for something like a lenolidomide maintenance and, and whether we should do that indefinitely versus a fixed duration like one to two years. That's another conversation that we can talk about that the Europeans might think shorter durations for cost effective reasons, but still observation maintenance was not at all standard of care in multiple myeloma. That being said, having that observation arm did give us some insight into how important is just DARA alone in maintenance. This is not using lenolidomide. So we'll focus on that second randomization. And with the most recent publication at 80 month median follow up, DARA VTD followed by DARA maintenance had a very barely significant PFS benefit over DARA VTD followed by observation. So to me that's very interesting. Continuing DARA forever essentially barely had a benefit over no maintenance at all. And that makes you wonder, well, if these patients get in such a deep state of remission, this MRD negativity that we are alluding to. This, to me, kind of hints at that, right? That there's probably a subset of these patients that who may not even need maintenance or may need a shorter term maintenance, but DARA barely beat Observation. That was an interesting finding in the study. And there was no OS advantage. Obviously. You know, we have effective salvage regimens at relapse nowadays. Interestingly, the VTD induction arm who then got DARA maintenance had the same PFS as DARA VTD followed by DARA maintenance. So what's interesting about that is it just seems like you just need DARA at some point. Right. Whether it's at the beginning or in maintenance, it kind of normalized the outcomes there. It's not really relevant to our patients who are getting a quad induction with lenolidomide. But still, it is very interesting finding from that. So this doesn't answer the question about overall survival.
- [09:32]
C
Right.
- [09:32]
B
What we care about in maintenance, are we subjecting these patients to toxicity? We want to make sure that they have a functional cure or operational cure where even if they're on maintenance, they're at least living longer. Right. Because if you're on observation, you're definitely living better cause you're not on maintenance therapy. This really kind of didn't help us understand do we need DARA maintenance at all? But it really just said dara and maintenance doesn't add a whole lot when you get a quad induction. I think that's fair to say that as the outcome of this study, it doesn't say don't do any maintenance, but it says DARA alone adds a little bit. So to me, I would not give a patient DARA alone in maintenance kind of based on this data. And just in general, we just have more data with lenolidomide that Sean had talked about. So Sean, what about those in the Perseus trial who got a quad induction with Dara vrd.
- [10:15]
C
So the Perseus trial really shapes a lot of how we think about our induction, as we've already talked about in our earlier episodes. And the design in the Perseus trial as a result also shapes how we think about the maintenance phase. So in Perseus, again, this is the transplant version of this trial. There is also the Cepheus trial in non transplant patients, but we'll focus on Perseus for right now. So in Perseus, all the patients who received daratumumab upfront in their induction then went on after their transplant to get maintenance with both Daratumumab and Lenalidomide. They continued this for at least two years. When they got to the two year mark, patients then were reassessed for their MRD status as they already had been at earlier time points. And for patients who had been able to reach an MRD negative state and had sustained that MRD negativity for at least 12 months. Those patients were able to stop daratumumab and just continue with single agent lenalidomide alone until disease progression or until intolerance. If patients were not able to achieve sustained MRD negativity so they were still MRD positive, for example, those patients were instructed to continue with both daratumumab and lenalidomide until disease progression or intolerance. Roughly about 64% of the patients in the daratumumab army were able to come off of daratumumab at the two year mark and then continue with lenolinamide monotherapy for the rest of their maintenance. For the rest of their maintenance. Because they were able to achieve that sustained MRD negativity that we've talked about seems to be one of the most important prognostic markers. Still though, this trial doesn't answer the critical question that Castiopia somewhat tried to answer, which is do patients really need both daratumab and lenalidomide versus just lenolidomide alone if they already got an anti CD38 upfront as part of their induction? So do you need it both in induction and maintenance or is just having it in induction or just having in maintenance, is that enough to get really the most bang for your buck out of these anti CD38 agents?
- [12:18]
B
These are two interesting studies. Both are quad versus triplet studies. To me, Perseus did the right thing at least to have some stopping criteria of Daratumumab. Don't give DARA forever because to me that seems insane and DARA is a medication. So I want to point this out as we talk about our cell therapy and relapse refractory episode. We have teclistamab plus daratumumab in the relapsed refractory setting with outstanding outcomes. And I've always wondered if you're on dara, on Dara, on Dara. And now the patient progresses, meaning the refractory to Dara, we probably shouldn't continue DARA in that patient, right? They're refractory to Dara, Dara after Dara. If patients are refractory, doesn't make a whole lot of sense. And so I wonder, are we selecting for resistant DARA patients? I mean, this is all conjecture, right? And I want to be very clear about that. But it really does beg the question, do we need DARA forever? Does the cost make sense for that when we have these really, really good Durable benefits. And we do have upcoming studies that will answer that question. A SWOG trial that will actually answer the question Dara R versus R maintenance. But it'll take some time for that to read out. In the meantime though, Ronick, we do have some data for an MRD adapted trial with a quad induction. I want to talk about this before we get to the Auriga trial and I'll let Shawn talk about that one. But Brenna, can you talk about the master trial? And we have Master 2 ongoing. But let's talk about the original master trial. Yeah.
- [13:31]
A
So the original master trial, Dara krd and as Vivek mentioned, it's a risk adapted MRD approach to determining maintenance strategy. So all patients got Dara KRD and then that was followed by an autologous transplant and then they got more Dara KRD in consolidation if they did not have sustained MRD negativity at at two time points. So those who had MRD negativity went on to observation without any maintenance therapy. And ultimately the results showed that standard risk patients could reasonably undergo a risk adapted MRD approach to discontinue maintenance. There was a low amount of resurgence of MRD at one year off of therapy in that trial. But specifically that was the standard risk patients. Nobody with higher risk disease.
- [14:16]
B
And you know, the high risk patients in that study, a lot of them relapsed quickly. And so that's why we're not saying that, hey, I would not use the MRD approach necessarily in that high risk patient. We really want to keep them in remission for as long as possible. And maybe that's the patient that you are thinking about. Daraa maintenance. You know. Yeah, we don't, we're talking about all the nuances here. We have an OS benefit from that meta analysis that Sean had started. But that high risk patients, I'm really thinking about that Dara R maintenance. But Sean. And we'll talk a little bit more high risk here in just a second. But Sean, can you tell us about the Auriga trial, which did actually randomize patients to Dara R versus R, but it wasn't perfect. And tell our listeners about that study.
- [14:50]
C
This is a relatively recent trial. So this was published in the last year or so. The Aurica trial enrolled patients who did not get daratumumab upfront in induction. So these patients were on regimens such as VRD and got four cycles of induction followed by autologous stem cell transplant. So in this trial, the patients that were enrolled had to be at least in a VGPR or better, but at the same time they also had to be at least MRD positive. So so essentially these are patients that completed their induction, had a pretty good response, but still had detectable disease at an MRD level. 200 patients were then randomized to either daratumumab plus lenolidomide maintenance versus single agent lenolidomide maintenance. And probably to no one's surprise there was more conversion from MRD positive states to MRD negative states in the combination arm using Daratumumab plus Lenalidomide and this was about 50% compared to 20% in the single agent Lenalidomide arms. The 30 month PFS rate was also roughly 80% in the Daratumumab and Lenalidomide arm versus compared to just about 65% in the Lenalidomide arm. So this still doesn't answer the question for patients who got quadruplet induction, but at least it does give us more evidence that if you were not exposed to an anti CD 38 agent upfront in your induction, you probably should get it as part of your maintenance, which combined with lenalidomide in that scenario let's
- [16:13]
B
take a moment to learn more about
- [16:14]
C
the sponsor for today's episode.
- [16:16]
B
Fellowship is intense and some questions are hard to ask. Google and AI can't give you real world practical advice from the front lines. That's why there's premium a trusted space where you can ask anything confidentially or by name and get real one on one answers from over 100 top oncologists in the country. From tough cases to new data to career choices, you'll get guidance you can count on in hours, not days. It's personal, it's trusted and it's completely free. Sign up today at Primum Co. That's P R I M U M co. And one bonus, I'm actually on premium as an expert. So find me and ask me a tough question. Just to recap here because I think this is important to me. Both Cassiopeia and the Auriga trial told me that as long as I get DARA at some point I do really well, right? When you look at Cassiopeia, the VTD arm, the triplet induction arm, once they got Dara and maintenance, it seemed like they did just as well as those who got quad induction. When I look at this Auriga trial again, they got triplet inductions, they were MRD positive who were enrolled and they were randomized to Dara R versus R. Those who Got Dara R maintenance. That reflects the Perseus trial. To me, that 30 month PFS rate of 80%, that looks like Perseus. To me, that looks like those who got a quad induction. So that kind of helped me understand, okay, we definitely need to be giving daratumumab to our patients in the frontline setting. There's no doubt about that. What it didn't answer though was that although the Auriga said that okay, Dara at some point in induction and maintenance is better than no Dara at all, it doesn't ask us, do we still need that Dara long term Perseus just kind of said, hey, no matter what, let's keep the profit margins from Dara going. Let's just give it for two years no matter what. And, and we have ongoing studies that will flush out this answer. I don't mean that in a critical way. It's just, it's just unfortunate that we didn't have that second randomization right at maintenance. That's what we really wanted to know. Don't just continue Daratumumab randomly, just randomize. At that point, I think a lot of us wanted to know that answer. We have the data where we're at. So, Sean, before we talk about high risk, how are you managing your patients when you're giving them a Perseus approach? Right. Dara, VRD is probably the most common regimen that we're giving most of our patients. We what do you do in maintenance and do you check their mrd?
- [18:27]
C
Yeah. So I think this is an interesting question. I'll preface this with a caveat that I think that if you ask different myeloma experts, you're probably going to get a little bit of a different response. And that's honestly okay because again, we all are working with similar data, but sort of how we interpret that data and how we apply it to our patients may vary because again, the data is not perfect. We don't have data that perfectly applies to really the exact questions that we're trying to ask, which, as Vivek said, is if a patient already got daratumumab upfront, how much benefit do they really get with it in maintenance? And if so, if they benefit, how long do you need to give it for? So I would still check MRD after transplant and then continuing to check it with probably yearly bone marrows after they've been in their maintenance. I think the way that I would approach it would be to stick close to what Perseus did. So in my patients who are able to achieve sustained MRD negativity once they're at the two year mark. If they're sustained MRD negative, I would probably stop the daratumumab at that point. And then I would continue with single agent lenalidomide as we'll probably talk about in a little bit. There is some data that is looking at the specific question of can you use MRD status to help decide which patients may be able to stop all of their maintenance regimen. But again, that's going to be a little bit more of a individualized patient centric conversation. And, and so I'm looking forward to talking about that a little bit later on in this episode.
- [19:46]
B
Now that you mentioned that, let's just talk about it now. So let's talk again. We'll table the high risk discussion for now. So we have our patient Shawn Dara, VRD auto Dara R maintenance for two years. You had mentioned check it after transplant, check it yearly. So now they're MRD negative, let's say, and they're on single agent lenolidomide maintenance. Can you tell us a little bit about, you know, we have some data, particularly the MRD2 stop trial. Can you tell us about that data and where the field might be heading as we look to some of these approaches of just coming off maintenance? Remember, the master trial just said keep on giving Dara KRD consolidations and then once they're MRD negative for a while, just stop everything. And it looked pretty good. So can you tell us a little bit about the MRD2 stop trial and other data in this space and how you incorporate that data into your practice?
- [20:31]
C
I think there are probably two main studies that I think about in terms of using MRD as a way to guide possible maintenance discontinuation. First, the first trial is this MRD to stop study that Vivek mentioned. And so this was a single center trial that was published in 2024 in the Blood Cancer Journal. This looked at 47 patients who were MRD negative by both flow and by Clonaseq. And this was at the 10 to the minus 6 level. So less than one in a million cells in their bone marrow had myeloma. These patients were sustained MRD negative for at least 12 months and were on lenolidomide maintenance. As part of the way that the trial was designed, they actually had an even more sensitive MRD test to help evaluate really how deep of a remission were patients in. But this was looking at the 10 to the minus seventh or less than 1 in 10 million level. And 80% of those patients were negative at 10 to the minus seventh, meaning that 20% of the patients, they had more than 1 in 10 million, but less than 1 in a million cells for myeloma. So in this study, these patients had lenolidomide that was discontinued and, and they were monitored for evidence of MRD resurgence. And so this is the idea that you are seeing detectable myeloma at the level of these minimal residual disease tests, but not necessarily outright progression based off of the IMWG criteria. In this study, the median time on maintenance was about three years. Disease resurgence. So this was defined as MRD being positive at the 10 to the minus 6 level. This occurred in 11 patients, so about 23% of the participants. However, only five of those patients actually had an outright clinical disease progression. One of the patients in the trial died from a second cancer, so not from myeloma. The three year progression free survival for this trial was 92% for the patients who were at that deeper level of MRD. So at less than 1 in 10 million cells having evidence of myeloma. So 92% for that group compared to 49% for the group that was positive at the 10 to the minus seventh level, but negative at 10 to the minus sixth at the time of enrollment. So this is limited by the small sample size, but what this really tells me is that the depth of negativity on mrd, so right now we're kind of limited by what technology we have, but the deeper of an MRD negativity rate that you have, so it's better to be less than 1 in 10 million than just 1 in 1 million or 1 in 100,000. That seems to also have a very strong connection with how well these patients do. So it's helping to refine a little bit of our understanding of mrd. How deep of an MRD negative status you have as well as the sustained MRD negativity, those are both probably important factors for helping to define which patients are likely to be able to stay in remission for a longer period of time if you were to stop maintenance.
- [23:12]
B
I think that's really interesting and I think kind of what you're highlighting here is that this is an ongoing area of research. Again, another plug we talked about in our last episode for clinical trial enrollment, multiple myeloma. We have new tools at our disposal. Patients are living for a decade plus. Why are we not going to give them a chance to come off therapy? And the only way to know that is through clinical trials. So it'll be really interesting to see where the field is heading. So now I want to pivot a little bit and let's talk about high risk patients. So let's say, remember looking at that new IMWG high risk criteria. So Ronak, we've alluded to the fact that in high risk patients the key to success is maintaining remission after transplant, that we can get them into a response, we can transplant them, but it's maintaining that remission that becomes challenging. These patients relapse early. So what is the maintenance strategy for these patients?
- [24:02]
A
One important thing to note is that only high quality trial level evidence is the use of single agent Revlimid post transplant. But we know that in general high risk patients have a median progression free survival of only two years. So these high risk patients can get into remission but don't stay in remission. And we don't have the ideal evidence simply because these patients comprise an overall small subset of the overall enrolled population. But we do have data to support dual maintenance with a proteasome inhibitor plus an IMID in these patients. Most would argue that these patients who probably need ongoing DARA R maintenance and the concept of PI plus IMID is less likely important.
- [24:45]
B
Okay, so listeners, if you remember anything in high risk dual maintenance approach is key in my opinion and I think the data supports that. Now we have this black box. We talked about how there's not much data for an anti CD38 plus linamide, for example, like Adara R maintenance and that for your high risk patients you're probably going to continue on that long term because we know they have shorter PFSs. And then there's some data for proteasome inhibitor and, and in IMID maintenance. So Rona, can you talk about the single institution Emory experience?
- [25:16]
A
Yeah Vivek, absolutely. And we'll link this study in our show notes as all the other studies as well. But specifically in this study they looked at 1000 consecutively treated patients from 2007 to 2016 treated with RVD induction. Patients with high risk cytogenetics got RVD maintenance after transplant. And what they found was that the median progression free survival was 40 months. So just over three years and the overall survival was 78 months. This was a significant improvement over other trials looking at single agent Revlimid which shows on average a median progression free survival of two years. So you know, again, these patients are getting much more maintenance therapy than what we typically treat our patients with in other trials. But it appears that using this more intensive regimen Seems to improve the overall progression free survival in these high risk patients.
- [26:08]
B
And that's what you'll see in nccn. We have things like Velcade plus revlimid maintenance, you know, Velcade plus lenolidomide maintenance for some of these patients. And we think about neuropathy, we think about toxicity that Emory experience. They also included dex. We now know that you don't need that much dex. I'll allude very briefly to the Forte trial and I'll let Shawn wrap this up. So we had something called the Forte trial, which you don't need to know the details. We'll put it in our show notes. But basically it was different Carfilzomibase induction strategies. And there was a second randomization of that study that after they got whatever induction strategy they had, whether they got an auto or more KRD consolidation, they were randomized to Carfilzomib lenolidomide maintenance versus lenolidomide alone. So PI imide maintenance versus PI alone in this case, not Velcade. We're using something like Carfilzomib. And the outcomes in that study, when we look at the high risk subgroup, the three year PFS was 70% for those who got KR maintenance versus 55% for those who got R alone maintenance. So what does that tell us? That maybe the PIMID maintenance is increasing our progression free survival in these high risk patients. We just don't have enough data. What do we do when we have a quad induction for these patients? How does MRD influence these patients? And so I think there's still an important evolving landscape for our high risk patients. Sean, can you tell our listeners a little bit about from your perspective, are you using a PI imid maintenance? Because it's in nccn. Now our listeners know why. Truly a single center Emory experience. That said, hey, it looks pretty good. Better than historical outcomes. And this Forte trial, again, none of these are modern induction regimens, but KR versus R alone seems pretty good. So Sean, how do you think about this?
- [27:45]
C
So again, I think this is an area where you're going to see differences in practice styles depending on who you ask and also which institutions people are based at. So there certainly are some institutions that tend to lean a little bit more towards incorporating PI as part of the maintenance strategy for high risk patients. Typically I don't routinely do that. So usually I'm sticking with Daratumumab and Lenalidomide for maintenance. I don't know that there's necessarily a clear right or wrong Answer here. So this is kind of, again, this is based off of experience from Perseus. And that's, that's kind of what I stick to. It's also knowing that there are options for us for patients who progress. And those options are increasing in that first relapse, whether it's including something that is, for example, Kyprolis based or for example, things like CAR T and now bispecifics as well. So at least as far as, from my perspective, I generally don't utilize PIs as for maintenance, but there are myeloma experts that do for those high risk patients. And there certainly is a valid sort of thought process behind why those were incorporated. Some of the challenges really can be, as we mentioned, some of the side effects that you can get, particularly with these patients being on one of these PIs for a longer period of time.
- [28:51]
B
I think, Sean, you bring up a very, very important point here. Right? It's that we still need to bridge our patients to something like a CAR T cell therapy and these high risk patients who relapse early. We'll talk about this in our cell therapy episode. An early relapse patient. I want to give them CAR T personally. Right. We have some of these patients. We want to do that. We need to bridge them somehow. And you don't want to burn all your therapies right now, particularly with these Carfilzomib, you know, really, really potent drug in the relapse refractory setting. By subjecting them to all of this toxicity, is that needed to improve the trajectory of their disease, to improve their overall survival when the data is objectively weak, honestly. Right. We have again, single center Emory experience, again better than historical norms, that 40 month PFS versus just two years. A lot better. And then we have the Forte trial, again, KR versus R maintenance. A little bit of more complexity to that because the high risk subgroup did really well, better than expected Overall. You know, three year PFS of around 50% in some of those patients is way higher than expected. The high risk criteria change constantly. So those high risk patients aren't the same as our current high risk patients. Right. And I think Sean really articulated it well. Look, the best data we have now is Perseus, you know, in addition to some of the other ESA Phase 3 randomized studies looking at quad inductions. And we should think about following those for now until we get better approaches.
- [30:07]
A
Guys, another fantastic episode. I think we covered so much information here, really laying the landscape for how we manage maintenance approaches in our myeloma patients and clearly we all have highlighted that there's a lot more unanswered questions in this space that are being answered as we speak. But it's going to take a few years for us to get that data. So an ongoing evolving space which I think has been the theme of the Myeloma series.
- [30:30]
B
And one thing I'll say what I really took away from this episode that Sean said is, look, let's follow the randomized data, which is perseus. And for now MRD testing has validity. Based on that trial, you can stop the Daratumumab at 2 years for sustained MRD negativity. And I think that's important for our listeners to know that that is a data driven approach to use MRD testing based on a phase three trial. Is it perfect?
- [30:54]
C
No.
- [30:55]
B
We wanted Dara R versus R randomization, but. But at least that's one thing to not give Dara forever. And I think that's really important for our patients to minimize toxicity and minimize harm.
- [31:04]
C
One thing I'll add too here, although some of the studies that we talked about are not randomized, they're sometimes single arm studies. That doesn't mean that you have to completely ignore the data. Right. So if I had a patient that came to me that was on their maintenance, maybe they're four or five years in, they've been MRD negative, sustained MRD negative, and they have no high risk mutations.
- [31:23]
B
And if that patient came to me
- [31:24]
C
and said, hey, I really don't want to take Revlimid anymore, I'm just kind of tired of it, I would use that data from those single arm studies like MRD to really help shape that conversation. Right. So talking with them about kind of some of the things that we know about that this person probably is at lower risk for having an early progression if we stop their maintenance. Again, we can't say for sure certain things, but I think it's important to know the data. That way you can use it to help explain to patients kind of what we sort of think about the based off their individual situation, help them to be able to make an informed decision about their care.
- [31:54]
B
It's so well said because it's going to take so long to get that OS difference. We're talking nine, 10 years for some of these things. Right. So I think, Sean, that's so important and so helpful really. I thought this episode fantastic. I hope our listeners got as much out of it as I did today.
- [32:08]
A
And it helps so much to have Sean who does this every day and hear your perspective about how you're applying this into clinical practice. So, guys, let's stop this episode here. And in our next episodes, we've got a whole bunch of new things planned, but the one episode that we didn't have in our prior Myeloma series that's on the docket for the future will be our episode focusing on some more exciting therapies like Bispecifics and Car T. So be on the lookout for that. But for now, until next time, we'll see you all later.
- [32:37]
B
See you later.
- [32:38]
C
See you later,
- [32:41]
B
Sa.