- Welcome, everyone. And thank you for joining the International Myeloma Foundation's "Living Well" webinar, Global Collaborations Bringing Us Closer to a Cure. I'm Robin Tuohy, Vice President, Support Groups. Today, we'll hear from IMF Chairman Dr. Brian Durie, who will share updates on the exciting IMF research projects that are happening globally through the Black Swan Research Initiative. This will be an hour-long program including time for Dr. Durie to answer questions at the end of this presentation.
To submit your question, please click on the Q&A icon that you see here on your screen, and we will address as many questions as possible. The IMF values your input, and we ask that you please take a moment to complete the survey, which will pop up on your screen at the end of this webinar. You'll also receive an email shortly after the webinar with a link to the survey if that works with your schedule better. We thank our sponsors for their support of today's webinar, and they are Bristol Myers Squibb, Janssen Oncology, Oncopeptides, and Takeda Oncology. And it's now my pleasure to turn this call over to Dr. Brian Durie.
- Well, thank you so much, Robin, for that kind introduction. It's a pleasure to have a chance to present details of the Black Swan Research Initiative, which has been a key project for almost a decade now. And so the project has been a huge success, and I think it's important to explain what we're working on, and what we have accomplished, and what we're expecting to accomplish in the coming months and years.
So before I start, this has been a very anxious week, I would say, for myeloma patients related to the passing of former president, former Secretary of State Colin Powell, who had COVID-19. Obviously, he also had multiple myeloma plus he had had previously, prostate cancer and unfortunately, was also suffering from Parkinson's disease. And so he was 84 years old. So clearly, a number of underlying risk factors. Unfortunately, for Colin Powell, a booster shot had been planned for him, but that was not accomplished before he became ill and was hospitalized.
But this does draw attention to the fact that myeloma patients are definitely immunocompromised and vulnerable with the two-shot vaccination with the Pfizer two shots, or the Moderna two shots, or the one-shot J&J. And so getting that additional shot, so it would be a third shot for Pfizer and Moderna and a second shot for J&J is extremely important in an effort to boost the antibody levels to a point where the protection is closer to where it needs to be.
And so we do have data that this does work and is a helpful thing to do. We're still studying what is the impact of some ongoing therapies, and to the extent that it's possible, taking a slight break in any therapies, well, around the time of the vaccination will obviously help your body to generate antibodies in a better fashion. Another really important thing to help protect all myeloma patients is if your family and friends that you're interacting with on a regular basis are vaccinated. And if they're elderly also, they can have a booster as well. And so this is quite important to have that protection around you.
And of course, with this Delta variant still floating around in the community, continuing to wear masks indoors and taking all of these other precautions that we've talked about so frequently continue to be important for the time being. And so I've written about this in a blog and also gave an interview on the TV for a San Francisco station, so that those details are also available.
So let me move ahead with the topic for tonight, which is the Black Swan Research Initiative. And so this was designed to search for a cure. Over the years, we've worked so hard to come up with better treatments for myeloma but we've never really had a collective project which was totally focused on trying to come up with a cure or cures for different variations of multiple myeloma. And so after having an initial brainstorming meeting, it was decided that these elements that I have on this slide here, slide number five were so important to move this project forward.
So we needed to understand the early onset of the disease. And this means the onset of the initial MGUS, the monoclonal gammopathy of undetermined significance, which I'm gonna be talking about that. I'll talk about MGUS, smoldering, and active myeloma, and try to clarify that for you, but early in the disease, there are opportunities to both prevent the MGUS in the first place but also to intervene to either prevent or delay progression from MGUS to smoldering and from smoldering to active myeloma. So we have this ability to intervene early and achieve best results, potentially, even to come up with a cure with therapies, and I'll touch on that.
If you are approaching management and treatment in this fashion, what you desperately need is a way to measure the level of the disease to track low levels of disease using minimal residual disease testing MRD, and this is a type of testing which is currently done in the bone marrow using molecular or Next Generation Flow techniques to see if myeloma cells are present or not with a high level of sensitivity, looking at a level of at least one out of a million cells or even better as you'll see, we're getting to be even better than that.
And the idea was that we would be pursuing following along on multiple projects at once to get better MRD testing, to study the immune reactions of patients related to being stable or not stable, a variety of projects which I'll touch on as I go through the presentation today. And so this diagram here in slide number six summarizes the course of the disease and the opportunities to intervene. So early in the course of the disease after a monoclonal spike has emerged, there are prevention opportunities which I'll talk about. If the disease has progressed a little bit further to the smoldering stage, there are opportunities for early intervention to achieve, hopefully, MRD-negative level, undetected minimal residual disease.
And this can be initially with smoldering myeloma. This can also be achieved in patients who have active myeloma. So the Black Swan Research Initiative doesn't just focus on the smoldering disease, it also is a strategy related to patients who have developed active myeloma and even at the point of relapse later in the disease. And so the next slide, slide number seven summarizes the IMF's global technology platform, and it shows you all the different places in the world that we have had the opportunity, the wonderful opportunity to collaborate with myeloma research teams in different countries to focus on areas of their particular expertise and interest. In Iceland, I'll spend some time talking about that. In Germany, their particular expertise has been in imaging.
And Jens Hillengass, who worked there for a number of years, he helped develop whole-body low-dose CT as an important technique and also studied MRI and PET scanning. We have completed a number of family studies in collaboration with the German team looking at are there familial factors, are there genetic factors that predispose to the onset of myeloma? And also looked retrospectively in Germany at the University of Heidelberg. They have a biobank that goes back 20 to 30 years. And so we can correlate patients who are, for example, MRD-negative now with what happened in the past.
In Spain, I would say this has been one of our major collaborations. The teams in Salamanca and Pamplona, very, very interested, as many of you know, in methods of detection for minimal residual disease with Dr. Bruno Paiva, Dr. Alberto Orfao, Dr. Jesus San Miguel, and Dr. Maria Mateos, Maria V. Mateos. We have moved forward with that team, and I'll detail some of our more recent work with them focusing on a shift from assessing minimal residual disease in the bone marrow to possibly being able to do that in the blood. And this is a very, very important step for the future. We have a whole network in Asia, the Asian Myeloma Network, where we do clinical trials and have centralized studies.
In Australia, we've collaborated with a group at the university in Melbourne looking at DNA mutations. And we have a recent project that I'll touch on in France. So to understand the focus for the Black Swan Research Initiative, it's important to understand the progression of the early disease.
Obviously, the first onset of the plasma cell disorder that we call myeloma is monoclonal gammopathy of undetermined significance, where the monoclone, the initial clone of cells emerges. And we have learned that this does include some early DNA changes, what we call translocations which are listed there. As you move forward, additional translocations occur involving mutations, involving chromosome 1, chromosome 1q, which is the bottom part of chromosome 1, and also deletions of chromosome 15, and that's the top part of chromosome 17, and then additional chromosome changes as you move forward with later disease.
And so it's important to be aware of, well, how do you know where you are in that spectrum? And so the IMWG in sync with the Black Swan Research Initiative, because really the Black Swan Research Initiative is a sub-project of the International Myeloma Work Group. It's one of the research projects. MGUS is obviously at that lower level, less than 10% plasma cells in the bone marrow, a very small low-level of protein, less than three grams, and no myeloma-defining events.
And so the first question is well, what are myeloma-defining events? And if you look over to the right in patients who have developed myeloma, myeloma is now defined by patients who have the traditional CRAB criteria that we talk about all the time, but greater than or equal to 60% plasma cells in the bone marrow of three light ratio, over 100 or better, or more than one MRI or a focal lesion with advanced imaging. Those three elements are what we call myeloma-defining events. And so there's none of that in MGUS. Neither are they present in patients with smoldering myeloma where the level of the disease is a little bit higher but less than 60% plasma cells and with some greater amount of myeloma protein in the urine. And so a key project that has emerged for the Black Swan Research Initiative is the project in Iceland called iStopMM.
Iceland screens, treats, or prevents multiple myeloma. And this is a screening project for the whole country, a population-based randomized study, which I'll show you momentarily. And so we've been so fortunate to be able to collaborate with Professor Sigurdur Kristinsson, and his team at the University of Iceland, and also the deCODE Genetics unit, which is affiliated with the university right there on the campus. And so this is a study where between 2016 and 2018, everybody over the age of 50, 40, excuse me, everyone over the age of 40 was invited to participate to find out if they had a monoclonal protein present in the serum.
The idea is to truly screen everyone who might be in that group most likely to possibly have a monoclonal protein. Over half of the population of Iceland agreed. Over 80,000 people and of those up to now, and it's increasing every day, 75,000 have been processed through this study which involves a lot of different testing, including blood testing, bone marrow testing, specialized imaging, collection of materials for the biobank, psychological questionnaires, and all kinds of other testing in what has become a very large MGUS clinic at the University of Iceland. And the Black Swan Research Initiative has been so pleased to be in the opportunity, have the opportunity to support this activity. We have recently published our initial results from 2016 to now, and we have this publication that just came out earlier this year, and you'll see that we've attached a link to this publication at the bottom of slide number 12.
And basically, it summarizes in more detail, the details that I've already shared with you in terms of the numbers, but also some of the initial findings. But the key finding that is emerging is that if someone is diagnosed with MGUS, then they have follow-up. This means that they will be under medical observation and care. And so dating back to 2015 with this particular article right here, patients who are under follow-up are less likely to have fractures, kidney disease, or increased blood calcium. And we know already that patients who are being monitored have a better outcome overall. And so one thing that is a backdrop for this that everyone just needs to be clear about is that 100% of cases of myeloma, so everyone who has myeloma, they have previously had an MGUS. And we learned this decisively.
This is a study that was published by Dr. Ola Landgren in "Blood" in 2009. And he showed that if you track back three, four, five, six, seven, eight years, you can see that that MGUS had been present, that monoclonal protein had been present in the blood often for many years. And then the progression often will happen slowly or sometimes more quickly at the onset of the myeloma. Now, this is all based on using serum protein electrophoresis. This is the crucial test for myeloma to measure the amount of protein that is produced by the myeloma cells.
And so here on this slide number 15, you can see that monoclonal spike over on the right at the top. The one on the left is albumin, and you'd think that might be the more important spike, but that's just the normal albumin protein. The one on the right is actually the myeloma protein, the M spike, and then at the bottom, using immunofixation, IFE, you can tell that this is an IgG lambda, IgG lambda monoclonal spike.
So what's happening related to the project in Iceland and overall is that we are introducing a new technology called mass spectrometry. And this is a specialized technique that can pick up the amount of a particular size monoclonal protein in the blood, or it could also do it in the urine or other fluids actually, but it's a very, very sensitive testing, which has been developed by The Binding Site company, and that there are actually other groups working on this. Right now in the United States, this is set up and available for testing at the Mayo Clinic in Rochester, Minnesota. So it's a practical commercial method. One advantage is that it identifies all monoclonal antibodies.
And so if you're taking Daratumumab, or Rituximab, or monoclonal antibody, that will be identified, and I'll show you that in just a moment. Since it's a more sensitive method, it will actually change the diagnosis. It'll allow us to pick up the original disease and relapse much earlier. It also will change our response criteria over time. Because of the sensitivity, we'll be able to detect the myeloma at a continued lower level and might be possible to track a patient over several additional months as they reach a deeper level of response. It will be an affordable test at $180. And so this just shows you diagrammatically on the top, the SPEP and the immunofixation. Immunofixation is in the purple dye.
Down at the bottom, I would draw your attention to the mass spectrometry, which is called mass-fixation or mass-fix at the Mayo Clinic. You see at the bottom, the big spike is actually the Daratumumab with the green arrow. The small spike is actually the myeloma protein. And you could see that could be a confusion if you didn't know that that big spike was actually the Daratumumab. And so this is quite important in monitoring patients on Dara at lower levels of disease. And so this will be a very important method that we are evaluating in several of our Black Swan Research Initiatives.
A little bit of an impact that we know already. If you're following a patient and the patient seems to be in remission, but then you run your mass spec testing, which we've done, in the blue here, you find out that with the mass spec testing, that the myeloma protein has actually not gone away. There's still a small spike. Those patients are the ones that would relapse. With the further testing, if there's no spike present, those are the ones that are continuing to stay in remission with a deepening response.
And so it is going to change the way that we look at this ongoing monitoring. And it also will influence the way that we look backwards. And this is quite interesting. This is from the data of Dr. Kyle from the Mayo Clinic, where he has data going back many, many years, which people are aware of. And he's been obviously extremely interested in MGUS. And overall on the right, he had a patient that was diagnosed with MGUS in 2016. He was able to check a sample from 1997, where he was able to find that that spike was actually there and detectable using mass spectrometry. And so using mass spectrometry, we're able to track back to see when and how the MGUS emerged. We have the good fortune to be collaborating with a group in France at the University of Nantes, and what they are doing to help understand this process is find out if the monoclonal protein, if the IgG lambda, for example, that's the spike which is in the serum that we're picking up, is it an antibody against some type of an infection?
And so what the group led by Sylvie Hermouet at the University of Nantes is doing is to see if the monoclonal protein, the myeloma protein is directed against some type, different types of infection. And she's found the answer to that question is yes, about 70% of the time, she's finding that the original triggering factor may have been an infection where the abnormal response resulted in ultimately the evolution of the monoclonal.
So we're quite excited about this. Infections include things like Hepatitis C, the H. pylori infection, Epstein-Barr infection, a variety of different infections. So we're now broadly screening a whole range of infections that could be involved. So quite an exciting side, kind of a side project that could be most enlightening. Now, another part of what we're doing is making sure that if we're going to be studying the impact of treatment, that everyone is using the same criteria for MRD. So is the MRD-positive or is the MRD-negative? And so Shaji Kumar led our IMWG effort, and the criteria for this were published in 2016 using sequencing, using flow, and then I'll show you in a moment, it's also important if there's any myeloma outside of the bone marrow. Since the MRD is testing the bone marrow, is there any myeloma outside of the bone marrow? And then of course, we wanna know is that MRD sustained over time at one year out to five years and beyond, which would translate potentially to a patient who could possibly be on the steps to be having a cure.
And so one of our collaborators is Dr. Elena Zamagni at the University of Bologna in Italy. And what she has done is look at the impact on outcomes of patients in a very, very precise way. So she's come up with a quantitative way to look at PET scanning to be able to say, is the PET scan positive or negative. And so she's shown that using these precise approaches, and she just published this rather recently, that having a negative PET scan, so negative uptake of sugar in any areas of possible myeloma outside of the bone marrow, that obviously is a good thing and the outcome is better. Next slide.
The other thing that that comes along with this is that we have been studying MRD systematically through a whole range of trials and a sub-project is where in our I-Square team project, we are submitting data to the FDA so that MRD could be accepted as an endpoint and the evaluation of outcomes for myeloma. But what you can see here, if you look at the collection of all the data related to MRD, and this is a paper that was published by Dr. Nikhil Munshi, he showed that across the board in different disease settings, MRD-negative patients, patients who respond very well and achieve MRD-negative, those patients do always significantly better than the patients who do not achieve that level of benefit. And so it's really two different risk groups. And so it's really a key endpoint that has emerged systematically from these Black Swan studies. And so the question that emerges is if we want to try to intervene early and achieve the best results, why have we not been systematically treating smoldering myeloma? Why have we been cautious about that?
Well, I think that we were obviously hesitant to treat patients who were not having any symptoms, asymptomatic, but then we realized that first symptom could be a dangerous one. The second point is that we needed to know better which patients with smoldering myeloma were really going to get myeloma soon. And I'll show you in a minute that we have come up with a better way of doing that. In the past, we didn't have treatments that really worked that well, and some of them were pretty toxic, but nowadays, we really do have highly effective and tolerable treatments.
And already, we do have phase III trials so that we need, we have now comparative studies where we can show that intervening early does have a good impact. So the first point, what are the factors that determine if a patient with smoldering myeloma will develop active myeloma soon. And over on the right here, the key things that make a difference are the height of the monoclonal spike, the monoclonal protein in the serum with a cutoff two grams. The free light ratio of 20 and bone marrow percentage in the bone marrow at 20%. So this is called the 2-20-20 system. And so patients who have that higher levels are in the higher-risk groups.
Now we've looked at this in a little bit more detail, developing what we call a risk score. And so the different levels have been given risk numbers, and then you can add up the different numbers. And depending on the total number of risk factors, then you can see what is your individual risk. And so we have identified the patients that we call at ultra high risk, and these are patients who have a score of over 12, and that's the top curve there. And you can see that over 70% of these patients will in fact develop myeloma within 18 to 24 months. Many of them within the first year, actually.
Over on the left, you can see that some of the factors that are more, most powerful in determining if a patient will be in that category are the percentage of the bone marrow plasma cells. You can see that the risk really goes up when you go to 30% or higher on the plasma cells. And also, if you have any high-risk chromosome abnormalities detected on fish testing. So now, we have a scoring system, we have a risk score, and we actually have an app which will be rolling out very, very shortly, where patients can actually, and doctors can load in the individual numbers, and you can generate your own curve to see where you fall in the risk category. But what we have learned from several projects within the Black Swan now is that treating patients who have high-risk smoldering myeloma using the 2-20-20 system or something very close to that makes a difference. And this is a study from Mary V. Mateos from Spain.
And this is a study with about 10 years of follow-up now. And the patients either received observations, so no treatment, or Lenalidomide, which is Revlimid and Dex. And you can see here pretty clearly that the length of the remission, the blue curve is obviously much better than the red curve, both in terms of staying in remission and the expected outcome with an overall survival observation beyond 7.8 years now in this particular trial. Note the study was limited by the fact that they did not use advanced imaging at that time. So some patients in the observation group may have actually had more active disease than we realized.
Now, another question is if you treat early, could that be a negative thing? So what Mary V. has looked at is looked at the overall survival in patients who progressed to active disease after treatment, after treatment. And so what she's found is that the patients who've had treatment, even if they progress, they continue to do better than the patients who were not treated initially. So there is a ongoing survival benefit which is in excess of two years, actually 2.3 years additional survival benefit with the early intervention. And so now we have other data. There's a Eastern Oncology Group study which looked at Lenalidomide versus observation. And again, you can see that the blue curve is better than the red curve. Patients who took Lenalidomide did better than the patients who were just observed.
And so we now have a number of questions. If we treat, maybe we should just be treating like myeloma. Or is it okay to maybe just delay progression? Or should we maybe be treating to try to cure patients? And I'm gonna show you data like that in just a moment. And if we're trying to cure, what is the best way to indicate that maybe we're headed in that direction, and of course, what will be the best length of the treatment? Can we stop the treatment if we think a patient might be doing well and potentially cured? Very, very important questions.
And so there is another ongoing trial in Eastern Cooperative Group where they're looking at what's called the Mye Regimen, which is Daratumumab, Len, Dex versus the Len, Dex. So they're kind of moving towards more of a myeloma-type treatment to see how that will work out but it's very exciting to see the results, which I'll show you now coming out of the first CURE trial from the Black Swan Research Initiative, the CESAR trial, where patients received Carfilzomib, Lenalidomide, and Dex. That's in the big blue box. And then they received high-dose melphalan with autologous stem cell transplant. They then received two cycles of Consolidation and then Maintenance with just Lenalidomide, Revlimid, and Dex for two years. So it's about a 2 1/2 year or so therapy, and then patients are followed off of therapy, okay? So where are we with that in terms of excellent outcomes?
And I think it's helpful to look here at the percentage of patients who achieve CR. So if you look at that one line "greater than or equal to CR," it starts out at 43%, 63%, 75%, 81% by the end of Maintenance are in a complete remission or better. And if you look at the patients who are MRD-negative, the patients who have no disease with careful testing of their bone marrow with minimal residual disease testing, 33%, 49%, 65%. So it's around 65, 62% have a sustained MRD-negative. And so this is fantastic. It also tells us that not all the patients are achieving MRD-negative, and so we have work to do, and I'll touch on that in just a moment in terms of what are we doing next within the Black Swan Research Initiative.
The CESAR trial, you can see here, tremendously excellent results. The remission at 90%, 92% of the patients are in remission, way out by five, four to five years. Overall survival, 96%. Really extremely good outcomes with this trial. We have now just finished accruing to the US trial, the ASCENT trial. Very, very similar trial. Patients received Carfilzomib, Len, Dex plus Daratumumab, and also for Consolidation, also for Intensification, and then through Maintenance. The total length of therapy again around two years. And we have our first patient who is now three years out on this study who continues MRD-negative. He's now been off of treatment for over a year and is continuing MRD-negative. And so we are quite optimistic that the number of patients achieving and sustaining MRD-negative will be higher in the ASCENT trial versus the CESAR trial. And so what should we do today?
Well, I think we're still studying this aggressive approach. For standard risk smoldering myeloma, we should be following them. For high-risk clinical trials or just Len, Dex possibly. And then if they are having multiple high-risk features, more in the ultra high-risk range, definitely could think about treating just as if it was myeloma since it is so close. Now, another area, which I hope can be very, very pivotal is the fact that we are assessing circulating myeloma cells. So this is something that we really haven't focused on much in the past, but when there is an active myeloma, the myeloma cells can be readily detected in the blood. And so if you have MRD-negative, then there are not plasma cells in the blood. And so we've been looking very closely at measuring the amounts of myeloma cells in the blood at very, very low levels. And this has been actually a big success.
You can see we've published several papers coming out of the Black Swan Research Initiative. To give you some concept, as of now, we've published over 50 manuscripts in research journals related to projects in the Black Swan Research Initiative. And so the idea is I don't want to go through all of the different projects that we are doing, but give you kind of the big picture. So what we're doing right now is that we have been using our best frontline options. And so what we call a quad, four agents, so a Daratumumab, Carfilzomib, Revlimid, and Dex, something like that could be considered a best frontline therapy. Somewhat better than 60% of patients will achieve MRD undetected with that.
We are now in the process of studying those patients who are MRD-positive, residual MRD-positive, or possibly biochemical relapse. So what is biochemical relapse? Relapse is where we have picked up evidence of active myeloma but there's no symptoms, no bone damage. There may just be a slight increase in the myeloma protein level in the blood. We may have picked up some low level of plasma cells in the blood. So early indicators of relapse without active relapse but we have the same strategy for this type of patient where we know that intervening early could give us the best results. And we're using very sensitive molecular and immune testing to evaluate these patients with the idea that one of our new immune therapies could be a way to knock out those early MRD-positive cells at an early time point. And we're obviously excited about the possibility of potentially using something like CAR T-cell therapy or a bispecific monoclonal antibody.
Some of these very powerful therapies are just a single monoclonal antibody, even a Belantamab combined with some other therapy. Some of these immune therapy cocktails that could make a big impact. And so there are a lot of opportunities that we see in the next few years for the Black Swan Research Initiative. The possibility of many new trials, the next phase will be to achieve MRD undetected at the point of biochemical relapse, early relapse. We are using much more sensitive testing. The group in Spain have developed an immunomagnetic bead approach such that sensitivity is down, not zero out of a million, but zero out of a hundred million, 10 to the -8. Then obviously, we have mass spectrometry, which picks up the myeloma protein at a very, very low level. And what's become quite important is serial immune testing. And so using our flow technology, we can pick up if there's any myeloma cell in the blood that might be MRD-negative. We can also pick up immune cells that are in the blood, so we could pick up CAR T-cells. If a patient has received CAR T therapy, so has been administered these engineered T-cells, then we can pick up are any of those T-cells in the blood potentially actively working against the myeloma?
And then of course, we're looking always at the molecular testing to see if some of the molecular testing can help guide us in terms of one therapy versus another. And so what are the goals looking like for five years?
And so I think that screening for MGUS will turn out to be something that will be useful. And that's because not only do patients with MGUS get myeloma, but they actually have a predisposition to a variety of other medical problems including a susceptibility to infection, development of neuropathy, kidney issues, cardiac issues, a variety of things, all of which we're evaluating as part of the Iceland project, the iStopMM. Now number two, we are definitely gonna be able to document that we have sustained MRD undetected or not in the protocols of our high-risk smoldering patients. And obviously, the ultra high risk, we'll be focusing on to make sure we do a good job with them.
And developing new interventions for the MRD-positive patients. And because we're involved in so many different studies in different parts of the world, we'll have many opportunities to confirm that different types of interventions and different types of monitoring are working well, and to confirm that the outcomes are continuing to improve, hopefully, dramatically in some cases with the introduction of new therapies such as a CAR T or active immune therapy, which could make a huge difference. And so you're definitely not alone. You have a huge team. Some of the ads that you see on TV, where they show you everybody that's working for you at the bank.
Well, at the IMF, there are lots of people working for you behind the scenes, and these researchers are working for you. But also there's a lot of work being done by Robin Tuohy and our team, and many members of the IMF team, where you can come to the IMF and help do well.
And so I'd like to, again, thank our sponsors, Bristol Myers Squibb, Janssen Oncology, Oncopeptides, Takeda Oncology, and we do have about 15 minutes left for questions. And so I'll try to go through those with Robin. And so Robin, perhaps the two of us can take a look and you can direct my attention to some of the more crucial questions, okay?
Thank you, all. I can see questions which I can start to answer. A smoldering myeloma patient is definitely qualified to get a booster shot. Obviously, myeloma patients related to age, the boosters are available for anyone over the of 65 but smoldering myeloma definitely would qualify as an underlying immune compromise.
- Dr. Durie, I see an interesting question about do the values or the amounts of MRD positivity matter? So might patients do well if they have sustained but low MRD-positive numbers?
- Right, this is actually quite a good question. What is emerging out of the longer-term follow-up already from the CESAR trial where we have patients out five, six years and beyond is that there are two groups of patients. Those that are continuing to be MRD-negative but 10 to the -5, 10 to the -6, or even deeper, so very deep sustained negative. But based upon the mass spectrometry and being positive at 10 to the -4 or 10 to the -5, some patients who've had an excellent response but are holding steady, and we're able to monitor those patients now using mass spectrometry. And thus far, a number of these patients are doing quite well. And so we are evaluating this group of patients as very, very important.
And for our new trials, we're really going to be focusing on patients who are not stable but are having, for example, biochemical relapse, but are actually relapsing. In other words, where the disease is clearly increasing. So we're going to be observing to make sure that we're not over-treating because being stable at a very low level can be absolutely fine, as I think many of you know who have been experiencing that. Right, and so I'm just looking at some of the other questions here. Yep, as far as I know, the vaccination does not cause a positive on the mass fix test. I haven't heard of that. Right. There's someone, I'm just picking these out where there could be a helpful question. So a patient is saying that they're taking 25 milligrams of Revlimid but I've been holding steady with a 96% decrease down to a 0.2 over four months.
Could they decrease the Revlimid dosage? And of course, this is really quite an important question. And because the blood counts can be impacted. There could be other GI and other side effects. And so definitely, talk to your doctor about maybe reducing the dose. It can be go down to 2015, even 10. And so to use Revlimid to sustain their remission for many years, it's often good just to reduce to that lower level. And actually, typically, in our maintenance trials, we use 10 milligrams as a maintenance.
How is a patient diagnosed with MGUS? The MGUS is just picked up where note, if it's picked up by chance, then it would be picked up just because the protein level in the blood is increased and then the doctor decides to run the serum protein electrophoresis. And so many patients are picked up with MGUS, basically by chance, when they're getting a little bit more of a detailed workup. In Iceland, we're actually screening. And so this is the big difference. So we're picking up what we like to call healthy people with MGUS. And so it's a big difference. If someone has come in to a medical center, and they're getting tested, presumably something's been wrong. And so these are people who have had some kind of a health issue, and then they're found to have MGUS. And that's actually quite different than a patient who is going about their business and is doing absolutely fine. And then we screen their blood and find out that they do actually have MGUS.
So I'm looking at here, someone who had the three vaccinations. Someone's asking, "They should have a fourth." We have no information about a fourth, okay? I think it is a good question. I think that we need to have some data. I think that several groups in the US and in Europe are trying to gather data about the impact of the boosters, particularly related to some treatments that... I know there have been questions about Daratumumab, for example. If you maybe stopped the Daratumumab for two weeks, or four weeks, or whatever, maybe the booster would have a stronger impact but the truth of the matter is that we don't know. And so I would not rush to get a fourth shot. I would hope that the third one will have some good impact.
Canadian patients, we're definitely open to Canadian patients, yes. Right now our trials have not, the CURE trials have not been opened in Canada, but we've been talking about doing CURE trials in our Asia Myeloma Network and would definitely be open to exploring opening trials in Canada.
Can the Black Swan Initiative lead to personalized treatments? Well, definitely, as we were just saying, with precise testing, we could pick up patients who are able to hold steady, but have a very low, low level of MRD-positive. What we're doing now right now, particularly with the group in Spain at the University of Salamanca is Alberto Orfao but also Bruno in Pamplona, they're looking at the immune status of patients who have low level and are steady. And we have some indication that they have a better immune system and maybe are holding the myeloma in check. And so we're trying to characterize that. So I think for sure, we will be able to personalize treatments based upon the detailed results that we come up with over time.
- Dr. Durie, I think it's interesting too. Sometimes patients are talking about the psychological impact. So for iStop-
- Yes.
- I know that they have been talking about if you're screened so early, and they are doing studies on that psychological impact.
- Right, this is another good question. People are concerned that, "Oh my God, I found out that I have MGUS." Well, actually, it turns out that in Iceland, they have been meeting with, and interviewing, and having a psychological follow-up on all of these people. And just to give you an idea, they picked up around 4,000 new patients with MGUS. And so there are lots of people coming into the clinic. And what they've found is that actually there has not been a serious negative impact. In fact, patients are happy to be under monitoring.
And in Iceland, a very nice aspect is that the Icelandic people have a perspective where they want to contribute to medical science. And so they are so, so thrilled to be participating in a study that can help. And so they have, in the background, a very, very positive attitude. But also, they have not been ending up depressed or having any negative consequences. Now, we're obviously continuing to monitor over time, but those results will be presented at the upcoming ASH Meeting.
And in fact, one thing I should have mentioned is that we're just so excited. The ASH abstracts will be released on November the 4th. However, coming out of the iStopMM, we actually have four abstracts that are accepted for ASH this year and four that are going to be oral presentations. And so look out for ASH where you'll have a lot of detailed follow-up coming. Will insurance cover smoldering patients? Now in our trials, obviously, these are trials where the drugs are provided. But one thing that I'm pushing for is that patients with ultra high risk, who fall into those higher-risk categories would actually be classified as a myeloma 'cause we're gonna be, I think, treating pretty much like myeloma. We're just coming in with our earlier intervention. And I think it's gonna be a whole lot easier if we classify the ultra high risk, in particular, as myeloma, and then immediately, that would be eligible for insurance coverage. Because I think that there have been questions about what is the coverage for smoldering and what about a patient who was treated in a trial? What do they have now? So that these are some important issues that we need to focus on and deal with.
- I see a really hopeful question, Dr. Durie. I think you could shed a lot of light on.
- Yeah.
- [Robin] Are we coming closer to a cure for those of us who have active myeloma?
- Right, right, I think that I did try to touch on this a little bit but we are very, very interested in studying MRD later in the disease course. And the reason for that is that with the CAR-T therapy, for example, in the CAR-T that's already approved by the FDA, over 20, 25% of the patients were MRD-negative. And these are patients who had relapsed refractory myeloma. And so introducing CAR T therapy, for example, to a patient later in the disease course could still have an MRD-negative achieved. And so we've been learning this in the last 5 to 10 years actually.
As we bring in newer and better treatments, patients can achieve MRD-negative. And so we should be... That's why we're looking at intervening at biochemical relapse. If we can intervene early later in the disease and someone who's relapsing and give them a decisive therapy, it may be could achieve a sustained MRD-negative. And so it's definitely something that we're looking at. I'm just seeing here. Yeah, so the different vaccines, I see these questions about the different vaccines.
People may have seen, and I think it is potentially important and relevant, is that if you've had a J&J vaccine, the booster raises your antibody four times. If you've had a Pfizer vaccine and you get the booster, it raises your antibody levels, I think, it's 43 or 46 times. If you have a Moderna, it raises your antibody levels 76 times. And so there is some indication that in terms of the antibody responses, certainly, the two-dose MRNA vaccines, the Pfizer and the Moderna are giving higher antibody responses versus the J&J. And so I think that it's very, very nice.
And the approval came through today for mixing and matching, where if you, for example, if a patient has had a J&J vaccination, it would be okay to go ahead and have a Moderna or a Pfizer booster. And personally, I think that that would be something for a myeloma patient to think about seriously because of that higher boost to the antibody levels. Yeah, I think that there's a lot of questions. I mean, one of the things about myeloma is that even if you're in remission, there is an ongoing immune suppression. And so I would recommend a booster for all myeloma patients and even some individuals, there are some who have developed COVID and fortunately, done really well. I would still recommend that these people get vaccinated because we know vaccination will give you better antibody levels and could avoid long term, what's called long haulers with the COVID.
When might we see data from the Iceland trial? Well, we'll get a lot of update at ASH. There's gonna be four oral presentations. So you'll have a lot coming out within the next month or so. Yeah, that Medicare, that there is a Medicare code. So that mass spec, if your doctor sends a sample to the Mayo Clinic, there is a coding for that. And so it's not a very expensive test. But it will be covered, I believe, okay?
- [Robin] And on that mass spec realm, Dr. Durie, questions are coming, how often should mass spec be done?
- Well, I think that it should be done right now just if there's a special question. So for example, I gave one example is that if you have a low level of myeloma and you've been taking Daratumumab, it could be good to do the mass spec to see if that spike is maybe just the Daratumumab. So it would answer a particular question. And so it's I don't think, we're not quite ready for the routine use yet.
We're trying to study the implications of having a negative and having a positive with mass spec but there are a number of like situations where you and your doctor might think, well, it could be nice to know is there a bit of spike left or not? So I wouldn't do it routinely right now.
- Well, I see we're really at the top of the order, Dr. Durie.
- Yes, we are, we are, we are. So I think that we've covered quite a lot of questions. And Robin, as you know, we are always happy to try to follow up, and people can call the InfoLine. And for some questions, we will definitely try to answer by email. We will definitely do that. So Robin, I'll turn it over to you to close for today.
- Sure, thanks, Dr. Durie. We really do have so much more to be hopeful for. This was such an excellent overview on all of the IMF global research and collaboration that really is so exciting. So as Dr. Durie mentioned, if you have additional questions, the IMF does have answers, and you could call the InfoLine, and that's Judy, Missy, and Paul. They're always happy to help you. And that phone number is 1-800-452-CURE, which is 2873. Or you can email them at [email protected].
And additionally, I wanna remind everyone tonight, as happy as we are that you've joined us here, we've got another really, really good program coming up, and that's gonna be on a Saturday on October 30th. It is a 7:00 a.m. Pacific and 10:00 a.m. Eastern program. It's a patient and family webinar that's going to focus on advances in myeloma treatments, what patients and caregivers need to know, of course. We've got a wonderful lineup of multiple speakers. We have Dr. Durie. Additionally, we have Dr. Adam Cohen from UPENN and Teresa Miceli from the IMF Nurse Leadership Board, Dr. Paul Richardson from Dana-Farber, and I will also be on.
So if you wanna register for this or for details, just go to myeloma.org. And also, don't forget. We did mention earlier at the end of this program tonight, we are gonna have that survey that's gonna pop up on your screen. We really do appreciate your feedback. So we'd love for you to do that. And most importantly, thanks to all of you for taking the time to be on this webinar. We hope you found it helpful to stay informed, and empowered, and hopeful for all our futures, and we thank Dr. Durie for breaking this really excellent, important, complex information down into things that we can understand.
And we couldn't do this without the generous support, and we're always grateful to our sponsors. And again, for tonight's program, that is Bristol Myers Squibb, Janssen Oncology, Oncopeptides, and Takeda Oncology. So Dr. Durie and everyone here, thank you so much.
- So thank you, Robin, and have a good evening, everyone. Thank you for joining us.
