Brian G.M. Durie, MD:
Welcome everyone to looking at results from Top Myeloma Research presented at ASCO and EHA this year. These meetings just happened earlier in June. A special aspect of this is that with me today, I have two patient advocates who will really be focused in on what is the relevance, what are the issues related to this research, very much from the patient perspective. So I'm very pleased to welcome Jack Aiello, who is a myeloma patient and a very active advocate from the Bay Area here in California, in the USA. So please welcome Jack Aiello. And very pleased to welcome Mira Armor, also a myeloma patient and advocate from Zagreb, Croatia, although I was just learning that, I guess, part of the time she actually lives in London, if I understood correctly. Is that right, Mira?
Mira Armour:
Yes, that's right. And I'm not a patient, I was a carer and then I became a patient advocate.
Brian G.M. Durie, MD:
Okay. Thank you so much. Anyway, welcome and we will really, really appreciate your input today. So let's go ahead here. Obviously, we always appreciate support from our sponsors. This week, we are very pleased to thank AbbVie, Janssen Oncology, Karyopharm, and Sanofi. And John from [inaudible 00:01:47] is going to discuss the audience Q and A to make sure that you have it correct. Do you want to go through that, John?
John:
Yeah, on your Zoom windows, you will have a Q and A button highlighted in that picture. And so, if you open up that window, you will get a place to type in your question and you can send it anonymously. There is an option on the bottom if you check that box. And then, any questions that we do not get to today, you can call the infoline at 800-452-2873 and then they can answer your questions on weekdays. And then, if you would prefer to send an email, you can also send an email to [email protected].
Brian G.M. Durie, MD:
All right, thank you so much for that, John. Okay. So let's go ahead. So we're going to focus on the ASCO meeting, which was held in Chicago June 2nd to 6th, the summit, which had some summarization and discussion of those results as well as looking forward to the EHA meeting, a hybrid congress, which was in Frankfurt, same place as the summit June 9th to 12. Now, one notable event this year, which I think was greatly, greatly appreciated by everyone in attendance was that there was an award ceremony linked to the IMWG summit where the Kyle Award was presented to Maria V. Mateos from Salamanca in Spain. And on the left of this slide, you'll see the very beautiful Maria V. Mateos with her chief and mentor, Jesus San-Miguel and myself. And then on the right, Dr. Tom Martin from the Bay Area, someone that Jack knows very, very well receiving the award in my name, the Durie Achievement Award. So that was just great enthusiasm for these two wonderful individuals, great researchers, great patient caregivers, very, very knowledgeable and compassionate in their care of patients. And I don't know if either one of them where you would like to comment about these awards. Any immediate comments, Jack or Mira?
Mira Armour:
I'll let Jack go first, as you know Tom.
Jack Aiello:
Yeah, we were just particularly proud of Dr. Martin from UCSF and we're enthusiastic about his award.
Brian G.M. Durie, MD:
Yeah, absolutely. Yeah.
Mira Armour:
And I think it's... I'm sorry. I think it's really great to see such brilliant hematologists so engaged and passionate about looking for cure because that's what we want.
Brian G.M. Durie, MD:
Yes, absolutely. And both are very much committed in that direction, especially Maria V. Mateos from Spain. Okay, thank you for that. And so, I think there's little doubt that there was one abstract, which garnished the most attention, and it was presented both at ASCO and EHA. At EHA, it was a plenary abstract. And at ASCO, it was part of a highly focused session on CAR T being used in a variety of settings. Impressive results, which we'll discuss a little bit where the use of the CAR T at early relapse reduced the risk by 74%, the risk of progression versus standard of care combinations involving, for example, pomalidomide and dara.
I think that in thinking about the outcomes for today's session, I think, it's helpful, and this is a slide that was presented at the IMWG summit, is to look at what are the results with the CAR T cell therapies and with the bispecific therapies, which are the new immune therapies. So obviously, the CAR T cell therapies are the T cells which are taken from the patient and engineered to attack the myeloma, and mostly for now against the B-cell maturation antigen, BCMA, on the surface of the myeloma. And in this particular slide here, you can see the two CAR T products which are approved by the FDA, ide-cel and cilta-cel, and the cilta-cel, which has got the tallest blue bar, which is almost up to a hundred percent is the one that is involved with the top abstract, the CARTITUDE-4 trial that we will talk about in a minute.
The ide-cel has also been presented in a similar light. And teclistamab, the bispecific, has already been approved by the FDA, and we'll talk separately about the bispecifics. But the main thing to pay attention to is, how dramatically better these agents are versus our current standards of care, which we have been reasonably pleased about. I would say, they're making quite a bit of progress. If you look at the far left, bortezomib and lenalidomide are the two blue bars on the far left, and the combination of those which give you VRd is actually the current standard of care in the frontline setting. And so, I think it's easy to understand the optimism of what could happen by using the CAR T cells or the bispecific monoclonal antibodies with teclistamab as an example, what could be achieved by using these earlier in the disease course.
And so, just thinking about that, how does that strike you, Jack, this point about expecting based on the comparison of the results so far?
Jack Aiello:
So I think about when I was diagnosed in '95 and a graph like this didn't even exist since we didn't have any of these treatments back then. So even when we got to 2003 and bortezomib or Velcade was approved and it showed like a 30% response rate and these others showed 30% response rate, they were very exciting and still are. But now to look at bispecifics and CAR Ts that show double or even triple those response rates, it's such a better world for myeloma patients.
Brian G.M. Durie, MD:
Right, right. And Mira, thoughts about this?
Mira Armour:
Yeah, the same. I mean, my mom was diagnosed in 2000, and I remember coming to a patient information meeting and just hearing about thalidomide and interferon, and thinking all these words. So I think for anyone coming into myeloma as a newly diagnosed in their family, this looks... I think it's a good time in a way to get a diagnosis, unfortunately, if you get it. But at least now there is so much happening and such good results, it's really exciting. So very good.
Brian G.M. Durie, MD:
Thank you. Yes, yes. And so the CARTITUDE-4 trial is basically that cilta-cel which was used in the relapse/refractory setting. So that those results, that blue bar that I just showed you, showing really excellent results in patients who have had many prior therapies. In this particular trial, the CARTITUDE-4, it was used in patients with early relapse and was compared with some standard of care therapies, mostly using pomalidomide or dara type therapy.
Sorry, I'm moving forward slowly here. And so, it was a phase-3 trial that was presented the CARTITUDE-4, so obviously two arms to the study. One group of patients got the standard regimen and then one group of patients... If you look on the right-hand side of this slide, it has the CARTITUDE-4 results, cilta-cel cell is the name of it. And you can see, if you look at the top line of the numbers, stringent CR and complete CR 73.1% versus 21.8%. So really dramatically higher deep responses with the cilta-cel versus standard regimens in this early relapse setting. And then, the ide-cel with a separate KarMMa-3 trial, which has been presented as well and published, not quite as good results, however, 39% versus 6%. So a dramatically improved outcome using the CAR T cells in the earlier disease setting.
And so, if you look at a graph of the length of the remission, the progression-free survival, the dark blue is above the light blue so far, so that the length of the remission is clearly superior. Keeping in mind that this was a difficult trial to do because it was done with what's called intent-to-treat statistics, which means that even some of the patients who did not end up getting the CAR T cells are included in that top blue curve. But setting that aside, clearly at 18 months, not only better than standard of care, but better than use later in the disease. So Mira, do you take this as a indicator that we really need to be looking at CAR T cells much earlier in the course for myeloma? Or what's your interpretation of this?
Mira Armour:
My interpretation looking as patient would do, I think, it would be better to use it in earlier lines. It's obvious. And I think, possibly, it'll be necessary to have it as soon as possible. I think patients are very optimistic that this will be accepted as a new standard of care instead of these other treatments which we have now, which were compared here, like daratumumab.
Brian G.M. Durie, MD:
Right.
Mira Armour:
So I think it's very hopeful and we just need to get data sort of tight enough so the FDA and EMA accepted it as a new standard of care in earlier lines.
Brian G.M. Durie, MD:
Right, right. Jack, I'll be interested to hear from you, but maybe you could also comment on the point that if we're looking at this as a standard of care, as Mira suggests, what about the problem of access and costs and things like that? Right now, for example, there's a struggle for patients with relapsing disease to get CAR T therapy that they might be eligible for.
Jack Aiello:
When I went over some of this with my local support group this past weekend, one of the major questions they would ask is, "Well, what about availability of the CAR T?" We have been told in the past that once you're eligible for it, it could be a six-month wait, and they may be in a situation where they don't have six months to wait. And now, bringing CAR T even earlier into the available treatment line, it may exacerbate that problem.
Brian G.M. Durie, MD:
Right, right. Absolutely. And some questions are coming in about: what will be the remissions and the survival with the CAR T? I would just point out that one little piece that's disappointing is that although the curve that shows the benefit of the CAR T versus the standard of care is much better, it still has that coming down. It doesn't have what we call that flat part of the curve where it seems like a fraction of the patients will maybe stay in remission for a very long time. And so, I don't know how that... if you had noted this particular aspect, Jack or Mira?
Jack Aiello:
Well, I wondered that previous slide showed MRD negativity as better. And I wondered, was there also information provided on sustained MRD negativity? I know you've always said that-
Brian G.M. Durie, MD:
Yeah, that's-
Jack Aiello:
... it has a certain length of sustained MRD negativity for it to really be effective.
Brian G.M. Durie, MD:
Right. And so, that really is what we're looking for and that will be coming. And we know for sure that sustained MRD negative. So what that means is if you're MRD negative and you're still MRD negative six months later or one year later, that really is something that translates into much better remission length and improved overall survival. And this is what we're looking for. So it's a little bit too early for that. However, on the scientist side, I think that we are still a little bit [inaudible 00:16:57] in the sense that we're still seeing that these curves are continuing to drop a little bit. In other words, we're not sure what fraction of the patients, the MRD negative patients will truly have a sustained long remission. And this raises the question of using different combinations, which was a big focus at ASCO and EHA this year: how do we combine to get overall fantastic results?
So maybe, I'll go forward just to give an idea of that. At ASCO, there was a main oral presentation session where all these different aspects were discussed. Abstract 8,000 through 8,008, looking at novel combinations and then bispecifics, CAR T, and then the antibody drug conjugate, the bela, and the new bispecifics. We don't have time to go through them in detail, but interesting that the combination of elotuzumab, a monoclonal antibody combined with KRd in newly diagnosed myeloma showed benefit, and using Kyprolis, pomalidomide, and dex was helpful as a maintenance for high risk myeloma, which is something that we'd be looking for.
We will talk about something very exciting, which is to combine the bispecifics. So the bispecifics are antibodies which attach to the myeloma through BCMA or another marker that we'll talk about in a minute, but also combined with the T cells in the microenvironment. So that's why they're called bispecific. One arm attaches to the myeloma and the or other arm attaches to the T cells. But then combining the talquetamab, which we'll talk about in a moment with dara, promising results, new CAR T cells, I would say I was especially interested in the CAR T cell data from Shanghai where they had a hundred percent MRD negativity in patients with high risk myeloma newly diagnosed. And then, of course, the new bispecifics Regeneron 5458 and elranatamab, the MagnetisMM trials. And some follow-on data with belantamab, which is currently no longer approved in the US actually, but follow-along data being presented.
As usual, there were many additional presentations at ASCO, looking at special populations related to age, disparities, renal compromise. There was a very nice session on Meet the Professor all about bispecifics with Philippe Moreau from France and Dr. Garfall from UPenn and a wide range of topics there. And then, at EHA, over 200 important abstracts. And so, as Mira was saying, these are very, very promising times. So many new observations, little details that can help guide day-to-day management for myeloma patients. Many unique presentations, each one with a special point that may turn out to be very important.
I was personally interested to see quite a focus on real-world findings. We see these percentages coming from the trials, but what happens when these agents or combinations are used with the regular doctor treatments? Obviously, looking at what the patients really prefer, the infections that occur specifically with the bispecific monoclonals, an interesting study that I had not seen before, looking at giving the Zometa the bone treatment for four years versus two years and looking specifically at outcomes for younger patients. So a lot of interesting data that contributes to our wealth of knowledge about myeloma. And so, I don't know if any of these different presentations or topics caught your attention, Mira or Jack, ones that we might not have time to talk about in detail, but maybe could be important.
Mira Armour:
Well, I'm very interested in real-world data as well because we know that the randomized clinical trials are limiting who can go into them. So in that way, we are not quite sure what will happen in real world when you have people with various other these illnesses, comorbidities. So I think there is a need of possibly changing or involving patient in the design of the new clinical trials to look at what is important to patient. Very often, we are here, patients here, PRO as a short... For patient reported outcomes, but actually we want patient relative outcomes. So there is lots of talk about involving patients. So I think with all these new molecules and different mechanism of affecting myeloma cell, we really want experts and clinicians to come up with some consensus on sequencing on in what order you should get any of these.
And also, the biggest problem, I think, for lots of countries in Europe, in particular in Croatia and in UK as well, I know it because I lived there for a long time, is the fact that patients are treated by protocol as it's called. So you have to go through all the drugs like bortezomib and lenalidomide before you can get something better. And I think that's why this clinical trial, CARTITUDE-4 is important because it's showing that in earlier lines, the results might be better. So once they are expensive, maybe the overall cost to the healthcare system will be less because people will maybe stay longer in remission. We don't know yet. We are hopeful. Patients are very hopeful that you will come up with Gleevec. So yes, that's my thought. I think definitely, there is a huge need for change how clinical trials are run, the data needs to be more accessible and used really, not wasted in some locked...
Brian G.M. Durie, MD:
Yes, yes.
Mira Armour:
Yes.
Brian G.M. Durie, MD:
So several very, very important points. I think that we do need to involve patients more in clinical trial design, I think, especially related to the bispecifics where with ongoing treatment with teclistamab, for example, the BCMA T-cell bispecific, there is a significant risk of infections, particularly pneumonia. And so, the length of the treatment needs to be carefully considered, can we shorten the treatment to reduce the risk of infection but still have a good treatment impact?
And then, of course, at the government level, this idea that you need to actually take all of the other therapies first before you can get the new therapies can make things very difficult in terms of access to some of the new therapies. And some of the new therapies are not even approved for reimbursement in many countries for many years or even at all. So any thoughts about some of that, Jack?
Jack Aiello:
Well, I had a variety of comments and questions on the past few slides. I thought a couple of those new CAR Ts, what was impressive there was that they were looking at [inaudible 00:25:59] manufacturing times and use the phrase, [inaudible 00:26:05] taking 10 days as opposed to four or six weeks, which is takes now, and sometimes that can be really difficult for myeloma patients.
Brian G.M. Durie, MD:
Yes, yes. So the rapid CAR dual target. So that could turn out to be a very, very important aspect to avoid the need for the bridging therapy. Yes.
Jack Aiello:
And then, I wonder on the eHow presentations, can you maybe share what EMD is, if you haven't already? And what is arginine deprivation? And then finally, was there a recommendation to take Zometa for four years rather than two?
Brian G.M. Durie, MD:
Right. That is a tricky one. Yes. I think that we need to just take a close look at that. It did show reduced progression in bone and did not seem to show an increase in the ONJ. But I think that my sense from talking to my colleagues is that people were thinking about taking a rain check on that before implementing that strategy, just not immediately jump to the four years versus the two.
Jack Aiello:
I wondered if they were maybe giving it every three months instead of every month.
Brian G.M. Durie, MD:
Yes. Yeah. Anyway, let's move forward. So the next couple of slides are pretty busy, but I think it's helpful to just see what is ahead. I mean, the immunotherapy timeline is just really incredible. There are the four arrows, the purple, the blue, and then the belantamab. Those four agents were approved by the FDA. So we have four immune therapies that have been approved in the last two, three years. But then, in the blue and the brown, we have all of the CAR T cells and all of the bispecifics, even trispecifics that are moving forward. And so, it's just going to be remarkable in terms of the options.
In the CAR T category, the middle one is GPRC5D, and this is that important secondary target on myeloma, which is a target for CAR T cells in this new study, as well as the bispecific. This is the target for talquetamab in the bispecific category. But other CAR Ts, the FAST CAR T, the even NK CAR Ts and AlloCAR Ts, which means that you could get CAR T cells, not your own, but from someone else. And then, all of the different bispecifics, each one seems to have perhaps some advantage, perhaps a little bit more efficacious or a little bit fewer side effects, these kinds of things as they're moving forward with the different CAR targets, BCMA, as well as the other targets.
It really is remarkable and it's hard to know how all of this will sort out over the next two to five years. Any thoughts about that, Jack? Just so many things coming forward.
Jack Aiello:
There are so many things. And I remember on one slide, Dr. Martin had a little icon, which with the words, "Not one size fits all."
Brian G.M. Durie, MD:
Yes.
Jack Aiello:
So my follow-up question to that would've been, but which size is best for me? And I wonder, with all the talk of AI in the world, will AI maybe be used to determine best sequencing and treatments for me and the patient.
Brian G.M. Durie, MD:
Well, this is a very good point. And Tom Martin actually is leading the IMWG effort in this immune therapy registries where we are actually gathering the real world data with the different immune therapies. We started with the belantamab actually, and now we have teclistamab as well as the CAR Ts. But we're trying to look at that in terms of what happens with one sequence versus another. And it may be that there is one very, very good sequence that works well and there be some very, very bad sequence or sequences where we should avoid giving some of these immune therapies in one sequence versus another. So that's the sort of thing that is going to be sorted out in the coming years. It's going to take a little bit of time. In the meantime, it does offer the chance of clinical trials with these different agents, and so many more patients will actually have access, which is a good thing. Any thoughts, Mira?
Mira Armour:
Yeah, I have lots of thoughts. Basically in Europe... I have millions of thoughts and I just want to find the solution. In Europe, we have such low accessibility to CAR Ts. There is lots of [inaudible 00:31:43] but there are institutions who are trying to produce academic CAR T. Because there is no, as they call them slots for changing these T cells and returning them to patient, that lasts I think about five, six weeks. And maybe you can explain, I mean, they're mentioning bridging therapy, which needs to be quite good, and infection needs to be low before you get CAR Ts. And as Jack said, you really want to know that you are choosing something which will fit you best. Looking at the previous slide, I mean, you can see from 2010 to 2026 plus, it says, with all these CARs and bispecifics, actually access to those is minimal. It's through clinical trials and clinical trials [inaudible 00:32:48]
Brian G.M. Durie, MD:
Yes, yes. Maybe, I'll just show the next slide actually. So the next slide is just to illustrate... I mean, this is going to be the situation coming up where these are going to be moving into these different trials with combinations, also looking at different lengths of regimens and things like that in the earlier disease setting for consolidation and maintenance, early relapse, as well as for some of the earlier work in the relapse/refractory setting. So just many trials, which... From my standpoint, it will mean that patients need to really talk to the doctor. And it seems like, this will be a very important time to get a second opinion with an expert to sort between one trial versus another. Yeah. So absolutely.
So let's go ahead. I want to have time just to talk about one of the new developments which could turn out to be the way forward for the future. And this is where the bispecifics are antibodies with two arms, one arm goes to the myeloma, one arm goes to the T cells using what's called a CD3 marker. On the myeloma side, it can be against the BCMA, the B-cell maturation antigen, or it can be against this new target GPRC5D. And the one that is involved with that is called talquetamab. And so this study, the RedirecTT-1 study combines simultaneously the anti-BCMA and the anti-GPRC5D. So the two different bispecifics targeting different parts of the myeloma in a one cocktail. And so, people were pretty amazed with the results of... The first results with this trial. And so, previous BCMA treatment was allowed. These were patients who were refractory. And a key point turned out to be that 32% of these patients had EMD, extramedullary disease, and 33% actually had high risk FISH testing results with the 17p type of changes.
The toxicity by combining these was pretty much expected with some significant infections. We know that can occur, especially with teclistamab, fatigue and also reduction in the blood counts. This was a dose finding study so that we're trying to find the ideal dose to combine these two bispecifics into a cocktail. And so, the results really pretty amazing overall response rates for the ideal combo, what's called the target dose or the maximum tolerated dose, over 90% responses with over 40% and the CR, stringent CR range. And so, really amazingly effective in this heavily pretreated population. And I think what caught people by surprise was the high response rate ORR, overall response rate. You can see here over 85% in patients with extramedullary disease, meaning soft tissue lesions outside of the bone occurring in different parts of the body, EMD. And so, in this particular trial to assess that, whole body PET/CT scanning was used to assess what turned out to be in many cases dramatic benefit.
If you look on the left, all these different dark spots in the shoulders and in the bones indicate soft tissue myeloma, some in bone, some in soft tissues. And then, over on the right, dramatic improvement with treatment. So this has meant that there is a huge interest in using this combination in relapsing high risk patients with extramedullary disease and, for sure, there's a new study looking at that specifically. But any particular thoughts about this one? Jack, did you have... I think people were pretty excited about the results with this.
Jack Aiello:
Yeah. Well, the response rates are equivalent to the CAR T-
Brian G.M. Durie, MD:
Yes.
Jack Aiello:
... for these off-the-shelf bispecific, so that's really exciting. Can you tell me a little bit more about infections? Because that's a concern, are prophylactics being given or dosages being adjusted, maybe fixed durations are being considered, all those are ways to maybe address infection. And do infections continue at that same rate while I'm on this treatment?
Brian G.M. Durie, MD:
Right, right. You're right. I think that Jack is raising a very, very important point. Yes, this is exciting, even close to CAR T, but the toxicity is definitely challenging. And I think the good news is that one of the leading investigators in this area is Dr. Ajai Chari, who is about to become an investigator at UCSF, is very knowledgeable and very, very interested in these things to try to adjust and achieve the best outcomes with this idea of compacted dose scheduling, reduced dosing as necessary to have the ideal combo with retaining efficacy as much as possible. And so, I think, it's fortunate for you, Jack, that you will be able to have direct contact and discussions with Ajai and the other team members, as these things are getting sorted out in the coming months and years. Mira, what did it strike you about these things?
Mira Armour:
I agree with Jack. It's very promising, but it's a bit early. I think we need to wait a little bit. Infections are a bit over worry. Patients need to be careful because they know they are very susceptible to them. What I found interesting is that the whole body scanning was used here, and I don't know how accessible whole body PET/CT is available. Is it available [inaudible 00:40:24]
Brian G.M. Durie, MD:
Exactly, exactly.
Mira Armour:
... because diagnostics are really important. And that's something, I think, we'll talk later on about as well.
Brian G.M. Durie, MD:
Exactly, exactly. Yeah. So there are a lot of implications to this, the toxicities, even the [inaudible 00:40:41] these are dramatic immune therapies which reduce the normal immune system as well. And could this ultimately increase the risk of second cancers as well as infections? This was discussed at our IMWG summit. And so, as you point out, Mira, this is early days. It's exciting, but we need to look at this carefully with a view to patient quality of life and patient preference and more patient input to some of these trial designs, for sure.
Mira Armour:
That's right. But the one thing which is important is [inaudible 00:41:21] effect on extramedullary [inaudible 00:41:26]
Brian G.M. Durie, MD:
Yeah, the extramedullary disease, yeah.
Mira Armour:
[inaudible 00:41:26] Yeah. That's it.
Brian G.M. Durie, MD:
Yeah, I think that Maria V. Mateos is going to be leading a follow-on study looking specifically at the extramedullary disease patients. I think that within that study, the whole body PET/CT scanning will be occurring fortunately.
Because of time, I'm going to keep moving forward. I think that one thing that's clear and we don't have time to go through this in a lot of detail, is that there are going to be so many novel immunotherapies, what will future protocols look like? And as you move forward from the frontline, maybe we'll use four drugs instead of three, what are called the quads, especially in the transplant setting. Maybe, we'll use the CAR T instead of the autologous stem cell transplant. And what we'll be using for maintenance will we maybe be using the new CELMoDs which are similar to IMiDs instead of Revlimid in maintenance, or maybe we'll be using some bispecific antibody combinations for consolidation or maintenance. And so, a lot to think about as we're moving forward, very, very active. And patients do need to be involved in trials to look at these things, which could be effective, but need to be acceptable from the patient perspective.
Just so that we have time, I want to just turn for the last little bit of time to some of the discussions that occurred at the IMWG summit because there were some important areas there. Maria V. Mateos did talk about smoldering myeloma where there is a lot of interest. And the main questions there are, number one, in what situation are we willing to go ahead and treat patients with smoldering myeloma as if they have active myeloma? I think the consensus right now is that there needs to be at least an 80% risk of progression in the next two years for people to be comfortable. If it's between 50 and 80, maybe something lesser could be considered. And certainly if it's less than 50, then we would observe or consider trials.
But maybe even more troubling because the outcomes for smoldering myeloma patients is potentially so good, how do we evaluate if we're making progress or if the therapy... One therapy is better than another? What are the correct endpoints? Should we just look at the length of the remission, the progression-free survival? Because the overall survival is going to be so long. And as Jack was pointing out a few minutes ago, sustained MRD negativity could be the way to go, and obviously we do need to look at quality of life, maybe more aggressive therapy versus not, how does that balance out.
So I don't know how you guys feel about treatment for high-risk smoldering myeloma. Obviously, the IMF and Maria V, we both conducted what we call cure trials, the CESAR trial and the SM trial, where we feel it's important to understand what can be achieved by treating high-risk smoldering myeloma, which is where there's a high risk of progression. Jack, do you think that we should continue with that strategy to achieve best results?
Jack Aiello:
So it's so logical to say that if we diagnose precursors, high risk precursors to myeloma earlier, then maybe we have a better chance of delaying progression to myeloma or even curing the disease. So I think it's really important to continue to assess whether that's realism or not, because there's still also the question of: how do you treat those patients with who have greater than 80%? Do you treat them with Revlimid index or do you treat them with the curative approaches, like you and Dr. Maria V mentioned? But I think it's really important... I mean, it'll be interesting to see one day if we even suggest that all patients over 40 or 50 should be screened for early precursors to myeloma.
Brian G.M. Durie, MD:
Right, right. And so, I didn't show it here, but obviously at the summit, we presented the results of screening, which does pick up these smoldering patients. And then the high-risk smoldering patients can be treated early. And so, you do have the chance from screening to jump right in and have an ability to prevent myeloma, to maybe cure myeloma. And so, there is a motivation, but we need to do it in a safe and secure way. Mira, how does this strike you treating high-risk smoldering myeloma?
Mira Armour:
Well, knowing what myeloma is and how it develops when it's high risk, I sort of feel like it would be good to do something-
Brian G.M. Durie, MD:
Yes.
Mira Armour:
... because you don't want it to just get out of control. So it is very good to know what's happening in Iceland with the Black Swan. They're screening everyone. I think there was a conclusion that there is no benefit in screening everyone, but if you have someone in the family maybe or you have or some other reason, then maybe it's worth screening and following it up, but otherwise not, but-
Brian G.M. Durie, MD:
Right. Good point.
Mira Armour:
... I think it's difficult one.
Brian G.M. Durie, MD:
Yeah, this notion was discussed, should we be screening? What is the value? And the iStopMM Black Swan Project is a randomized study looking at outcomes including survival. And so, until we have that information, we can't say that screening is appropriate. So we're waiting to see what is the value of screening. And it turns out that the screening could have values which extend beyond just myeloma, but really too early to know.
Let's just move ahead and then I'll try to touch up on some of the questions that are coming in. Yeah, mostly, we've answered some of these questions as we go along. One question was obviously, one advantage of the bispecifics is that they are off the shelf, and so they're going to be more readily available versus the CAR T, that's for sure. But one big advantage of the CAR T is that you get the CAR T treatment, and if it's a decisive treatment, then you don't need to be taking any maintenance. Some of the happiest patients that I have are patients who are MRD negative after one or two years following therapy where they're not on therapy. And this is tremendously attractive.
And so, using mass spectrometry and MRD to track these kind of patients is very much important. And this was discussed at the summit with an update from the Mayo and a commercialization update. I'm just going ahead just so that we can cover some of these points. But the main point for everyone to be aware of and especially patients, is that many labs will ultimately be switching over to use mass spectrometry to detect and to measure the myeloma protein level. And so, what's going to happen over the next year or two is that the results coming back from the lab are going to be showing numbers, which are the result of measuring the myeloma protein using this new technology of mass spectrometry. And part of that is on a test for test basis, it's much cheaper to do this with mass spectrometry versus the current methods with SPEP and other methodologies. Also, it can be used for detection of other diseases.
What you're going to be seeing, and just to draw this to everyone's attention, there is, what's called, a low resolution method for mass spec, which is called Mass-Fix by the binding site, this is called the [inaudible 00:51:17] method. This is the one that's most likely going to be approved for general use, but there's also a high resolution method, which is much more sensitive using a different type of machine called Q-TOF. And so, you're going to be hearing about that, because in patients who are MRD negative, this is probably the way using a blood test to come as close as possible to seeing if they are MRD negative. So this is a new technology that is going to be moving forward and potentially widely available.
We did talk about having various MRD testings approved by the FDA and Bruno Paiva from Pamplona, he showed these data here where we're looking at next generation flow in a bone marrow test as well as in the blood as equivalent to PFS. And so, the big thing that would be very important is that if the FDA would accept within a trial, randomized trials, that we could use the MRD testing results to indicate that one treatment is better than another. And you can see looking at this line here with the different trial dots, that in general, the results are pretty good correlation between MRD tests and the length of the remission. We need a few more trials to make this line really solid, and that's what we're working on right now. But it looks quite promising within the next year or so that there will indeed be an FDA approval so that we can use MRD as an appropriate endpoint within trials.
And then, there's also a scenario where using the next generation flow, the flow testing for MRD in the blood using blood flow, that we could replace some of the bone marrow testing with peripheral blood testing, and this would be really, really good. And so, the hypothetical scenario is that with mass spectrometry high sensitivity and with the blood flow using a high sensitivity method in the blood, patients can be switching in the next two, three years from a lot of bone marrow testing to maybe more blood testing, which is definitely pretty attractive.
But as this moves into clinical practice, right now, although there is tremendous enthusiasm for all of this, there are a number of issues that need to be addressed. There need to be proper guidelines: when should we be measuring that MRD test? How often should we be doing it? Make sure that we have a good sample, and make sure that the reports that are coming from the lab are reproducible and interpreted correctly. So a lot of different details that are coming along there in terms of testing with mass spec and MRD. In Europe, how do you see the use and the access to MRD testing? How do you see that as potentially available moving forward?
Mira Armour:
Well, at the moment, it's not everywhere. I think it's part of clinical trials in Croatia. Definitely, I know the feeling is that it's not in... It's not for everyday real patient. So I think the hematologist investigators need to get these guidelines on MRD really tight that it can be accepted by FDA and EMA, because we are all very, very keen. I think the patient communities behind you, we are keen to get something which will get reimbursement quick. No one... I haven't heard of one patient who said, "Oh, I love bone marrow biopsy. It's so lovely. I can't wait for another one."
Brian G.M. Durie, MD:
Yes, yes, yes. Yeah.
Mira Armour:
Yeah. So we really... I think good diagnostic, good cytogenetic testing and some personalized, not by protocol treatment, I think that should be the future. We should all get together with data [inaudible 00:55:48]
Brian G.M. Durie, MD:
Yes, yes. Yeah. Jack, any takes on these new testing methods [inaudible 00:55:53]
Mira Armour:
[inaudible 00:55:53] involving patients and what's important [inaudible 00:55:55]
Jack Aiello:
Well, I heard a whole bunch of patients applaud when you talked about testing via blood versus bone marrow biopsies, that's for sure.
Brian G.M. Durie, MD:
Right.
Jack Aiello:
I think what will help MRD testing, because still today, at least the centers I'm familiar with aren't doing it routinely, and they aren't doing it routinely because we're still in the trial mode to understand what we do with the MRD results.
Brian G.M. Durie, MD:
Exactly, exactly.
Jack Aiello:
So when we have that information, that will also help patients more easily access MRD and doctors more easily deciding to get MRD results.
Brian G.M. Durie, MD:
This is a key, key point, Jack. I mean, we know that MRD negative is a good thing, but what are you going to do about it? I mean, will you go ahead and stop the maintenance? If it's positive, will you go ahead and switch to some new therapy? We need the trial data to support that. And a number of questions have come in related to that point actually. And we just don't have sufficient information. Sustained MRD negative, we know is particularly good, but one new type of data that came along is that you can be MRD positive; however, if the pattern of the disease and the bone marrow is what's called MGUS like, if it's more indolent, it could be positive, but maybe the myeloma is not going to progress. And so, we need a little bit more information to help us use the MRD results in an appropriate way.
And so, it's still early days, although there's tremendous excitement about wanting to use it, and we know that ultimately it's going to be a powerful approach. The tests, the next generation flow will be approved in the bone marrow, as a test in the bone marrow within the next year, probably by early next year, and the same for the mass spec. In fact, the mass spec may be approved in Europe before the end of this year. And so, this is something that's going to be a reality in terms of results coming back from the lab in the very near future. And so, on the IMF side and the IMWG side, we're very, very keen to have appropriate guidelines in place, that's for sure.
And so, there were a lot of takeaways coming out of the summit, looking at the Registry as well as our Biobank, lots of publications guidelines planned. And as you can see here, some of these things we've been talking about are new areas of focus, looking at these infections, how do we reduce them, quality of life, the patient perspective, real world role of MRD and mass spectrometry. And the follow-up for us will be at the ASH breakfast meeting, always an exciting event. And so, talking of exciting events, a last thing that I will close with was something that was very special this year for the IMW Summit. At the award ceremony, we do have a band performance, which is led by our IMWG musician in chief, Vincent Rajkumar and Philippe Moreau, and mostly a group of lady investigators, which is lovely.
These ladies, I have to say, they mostly came together when Maria V. Mateos was awarded the Durie Award two, three years back. And they came together to toast to, what they call at the time, the Dancing Queen, which is Maria V. Mateos as it turns out. And so, this band decided to call themselves the Plasma Cells IMWG Band, and really very, very entertaining. And you can see that the different doctors are holding a piece of paper in their hand because they're telling stories about all of the different award winners over... Well, in Frankfurt as well as in previous years. And so, maybe, you guys can comment about your final thoughts about the band. How'd you feel about the band?
Jack Aiello:
They were fantastic. They put a lot of effort into the words and lyrics for these great songs they did.
Brian G.M. Durie, MD:
Yes.
Mira Armour:
They're natural, don't they?
Brian G.M. Durie, MD:
Yes, it is great. And I have to say that it was a tremendously busy schedule with ASCO and EHA, and this was in between, and they did not have a lot of time to practice and write the lyrics, and so tremendous kudos to this team that will be moving forward now with the Plasma Cells. Well, we need to worry that maybe the Plasma Cells will go off and have a separate career, although I don't think so right away.
Anyway, I think that that brings us to a close. The main thing I would like to say is that I'm sorry that we didn't get to all of the questions. I'm not sure when venetoclax will be approved by the FDA. There is a trial, results are pending of that. These questions that we haven't directly touched on, if you want to follow up with the IMF hotline by calling or emailing, please do that. And we will try to follow up on these questions as well. So thank you to Jack and thank you to Mira. Any final thoughts about these exciting times for myeloma patients?
Mira Armour:
Final thoughts? Keep on working. We need to keep on working. It's good. It's coming along. It looks very hopeful. We just need to get some consensus, some guidelines, get access to clinical trials by as many [inaudible 01:02:21] as possible. We need access.
Brian G.M. Durie, MD:
Definitely. Definitely. And Jack, any [inaudible 01:02:27]
Jack Aiello:
[inaudible 01:02:28] for patients, keep educated, go to a support group, watch these webinars, get a second opinion, investigate clinical trials because that's how the progress of myeloma treatments moves forward.
Mira Armour:
Yeah.
Brian G.M. Durie, MD:
Absolutely. Couldn't agree more. And this is going to be a very active period where this needs to be happening with communications between the patients and the doctors, the healthcare team, to really have therapy evolving from these many, many options right now.
So there will be a video replay available of our webcast today, and we do want to hear from the participants. And I'm just so sorry that we didn't get to all of your questions, but we will happily follow up as best we can. Okay. So thanks to everyone. We appreciate it. We've run over by a couple of minutes or so, but hopefully that's not a problem for anyone. Thanks so much, Jack. Thanks so much, Mira. I appreciate your time and your efforts input. Very, very valuable for everyone. Thank you.
Mira Armour:
Thank you for having us.
Jack Aiello:
Thank you.
Brian G.M. Durie, MD:
Thank you so much.
Mira Armour:
Thank you.
