Robin:
Hello and welcome everyone. I'm Robin Tuey, vice president support groups of the International Myeloma Foundation and it's my pleasure to welcome you to this webinar, top Myeloma Research presented at ASH 2022. What patients and care partners need to know. ASH is the annual meeting of the American Society of Hematology. On this live webinar, Dr. Durie, IMF chairman of the board and Chief Scientific Officer will summarize key takeaways from ASH that impact the myeloma community. Additionally, Dr. Durie will host a panel discussion highlighting the patient perspective with Linda Huguelet, IMF support group leader of Chattanooga, Tennessee, with Nick Lenoir, IMF support group co-leader in Brooksville, Florida. Both Linda and Nick were part of the IMF support group leader in-person and virtual team that attended the ASH annual meeting. They both attended in person. So this brings together the science and expertise from Dr. Durie along with that key important patient input.
So if you've not yet accessed tonight's slides, you can do so as always at myeloma.org. Additionally, to help you better understand some of tonight's slides, we have included links to myeloma terms and definitions and also myeloma acronyms commonly used. You can find these links right below the button where you downloaded tonight's slides on myeloma.org. So here of course, we're always very grateful to our sponsors. For this webinar, the sponsors are Bristol Myers Squibb, GSK, Janssen Oncology, Karyopharm Therapeutics, Sanofi and Takeda Oncology. At the end of this webinar and panel discussion, we'll take the time for your questions. Please send your questions by opening the Q&A window and typing your question right there. We'll get to as many as possible, but please remember you can always contact the info line at 800-452-2873 or by email at [email protected]. It's now my pleasure to turn this call over to Dr. Brian Durie.
Dr. Brian Durie:
Well thank you, Robin, for that really good introduction to give our audience a flavor of what we want to accomplish during this webinar. So the topics to be covered are listed on this slide, slide number four. I identified six topics that really were the most actively discussed, where there was the most expressed interest among the attendees at ASH with many sidebars and discussions and questions about these particular six topics. The bispecfic antibodies were, I would say, the highlight this year and I'll spend the first bit of time talking about those. The use of CAR T-cells, the engineered T-cells from patients, CAR T-cells, the use in the frontline setting is pretty intriguing. The studies from Iceland pretty remarkable. There were actually 10 presentations from this one project. The iStopMM Project Iceland Screens treats or prevents multiple myeloma, led by Dr. Sigurd Christensen from the University of Iceland. This is also a program that's supported by the Black Swan Research Initiative.
The ASCENT and the Cesar trials, it was great to see them presented at the same ASH meeting. Both of those are aggressive approaches to the treatment of early disease, high risk smoldering myeloma in an effort to achieve the very best and deepest responses and hopefully have a chance to cure some patients. If you're looking to cure patients with myeloma, the first step is to look at MRD, minimal residual disease, and to achieve a zero level if you can. So especially interesting to discuss two abstracts dealing with ultrasensitive testing and introducing the role of Mass Spectrometry. I'm glad that Robin mentioned the glossary and the terms because as I go through, there will be some terms, like MRD and the like, where it might be helpful just to double-check what are the meanings of some of these words. I think from a patient standpoint, the protocol from France, the IMF study, looking at a comparison where dex was removed from one of the treatment combinations is pretty interesting, dex sparing.
Okay, oh, first of all, we have quite a range of resources related to ASH and these are available here. I wrote a text summary of what I'm going to present right now in a blog form that was posted. IMF support group leaders, like Linda and Nick, have their perspectives in the form of blogs. We also had a comprehensive symposium at the Friday satellite session and we also have done the IMWG conference series and there are ASH abstract summaries. One abstract or presentation that we won't have time to talk about much is building dietary evidence for hematologic malignancies. So I would recommend people who are interested in the impact of diet, that they could check this out. This was quite an interesting presentation.
Okay. So the first topic, these bispecfic antibodies, and this was I think the most discussed of these bispecifics, Talquetamab. It targets, not BCMA. When we talk about these antibodies that target the myeloma, we're normally talking about B-cell maturation antigen, BCMA, because that's the most commonly expressed. Now there has come up interest, if people are using the BCMA as a target, what about alternative targets? So I think that's one of the reasons there was particular interest in this G-protein receptor group and with the linkage to the CD3 as a bispecfic. So this particular abstract was presented by Ajai Chari, and I would have to say he did really an excellent job in explaining the different details of this particular trial.
So just to understand what exactly is this Talquetamab? If you look at the diagram over on the right, you'll see that this Talquetamab has two arms. It has that green arm, which is targeting the GPRC5D target on the myeloma. Then it has the combo with the orange, which is targeting the T-cell, which is in the micro environment, using this CD3 receptor. So by bringing the myeloma and the T-cell together, this activates and enhances the achievement of myeloma cell death in this local micro environment.
Overall, the reason that there was such an excitement about this is that the overall response using this type of an antibody has been in the 64 to 70% range using weekly or every two weeks type of a schedule in this protocol with a play on words monumenTALquetamab-1 study. This study was also interesting because it did look at patients who had had previous targeted therapy. So looking at the specific benefit with this GPRC5D bispecfic.
A particularly interesting and important part of this monumental trial was looking at the overall response rate and the duration of the response with two doses of this antibody, the 0.4, which is on the left, and the 0.8, which is over on the right. The interesting thing is, if you look at the response rate, you'll see overall response rate 74.1% and 73.1%. Then the duration of response rather similar with the two doses. So this is quite important because it gives you some flexibility. If you have some toxicities, you don't need to be so worried that you need to keep pushing to that higher dose because actually the lower dose does have a strong efficacy. Then of course the duration of response is out in that seven and a half to nine month range all the way out to 11.9 months. So really very respectable lengths of response or remission.
So the summary on the Talquetamab in this monumenTAL trial, very active, overall response rate, 73 to 74%. These are in heavily, heavily pretreated patients. In patients who had had prior T-cell redirection therapies, the response rate 63%. So very respectable with acceptable safety and other measures. Now there are special side effects with Talquetamab where it can affect the nails and the skin, and you do need to be careful about diet because patients have a tendency to lose a little bit of weight. So you do need to watch out for some of these unusual side effects. As I mentioned, those adjustment is possible without actually stopping the treatment. This is sufficiently well tolerated that now combinations are being looked at to see how well this could do in combinations with other drugs like daratumumab or IMiDs and the like. Very impressive. 70% or better response with this new bispecfic.
Now, there were half a dozen different bispecifics presented at ASH. This shows that the listing, most of them as you see directed against the BCMA, the B-cell maturation antigen. A couple, one, the Talquetamab and then also Cevostamab against another target FCRH5. Very high response rates, but the Talquetamab really quite impressive.
A concern, particularly with the BCMA bispecifics, is the risk of infections. So you can see in the one column in the red box over toward the right as high as 68.1% infections. My sense, from listening to Dr. Chari, is that the infections were less of a concern with Talquetamab. Of these other antibodies of note, the ABBV BCMA targeted bispecfic does not require a step-up dozing, which is good. It makes it more manageable, where you don't have to come into the hospital necessarily to get that step-up dozing schedule.
So this was a big area of discussion and excitement at ASH, thinking about these what are called off the shelf products. So the big thing here is that you can go into the clinic and you can get the bispecfic antibody versus the CAR T-cells where several weeks are required for manufacturing. So this is a very attractive feature. So I'll be interested to hear how our two patient guests reacted to this information at ASH. So maybe Linda, you could comment first. What was your impression about all of this?
Linda Huguelet:
Well, it's very exciting to see such new ways of fighting myeloma. I'm a 12-year patient and I've been going to ASH for 10 years. The advances in that decade have just been amazing. This is exciting, although from a patient perspective, the side effects are definitely, I'd say, a bump up from what myeloma patients are used to. In my situation, I would be treated most likely in a community setting. So I know they're working on protocols for how to administer this, perhaps with hospitalization in the community setting. So those are all things that would be very important for me to research as a patient if and when this became an option for me.
Dr. Brian Durie:
Right, right. So very good points there. Nick, how did this strike you?
Nick Lenoir:
So two things really stuck out. One was the ability to adjust the dosings. I mean, they had proof that if you were starting to have the side effect issues, you could drop down in dosing where you wouldn't have to go off treatment. Two was the OR. I mean, just in the highly treated patients, that could be some of our, that have been heavily treated, next step.
Dr. Brian Durie:
Absolutely.
Nick Lenoir:
So to me, it was just great to see what's next.
Dr. Brian Durie:
Absolutely, absolutely. I see the questions here. It is given subcutaneous and there were schedules once a week or every two weeks. Yeah. So just to answer that question. Now, both Talquetamab and the BCMA bispecifics, they have the same activity where they both bring the T-cells close to the myeloma. In the one case, using the BCMA on the myeloma. Then in the case of Talquetamab, the other target on the surface of the myeloma.
All right, so very, very exciting and I would say most of the discussion seemed to be... To give you an idea for this particular presentation, there were five overflow rooms of people who wanted to get in to listen to this. So it gives you an idea of how popular it was.
So at this particular ASH, CAR T-cells. So this is one place where that glossary could come in handy because I don't have time to go into all of the details about the CAR T-cells, but I will discuss it a little bit related to one of the abstracts. So not so much follow up overall about the CAR T-cells at this ASH, but I want to highlight the one abstract where the CAR Ts were given to newly diagnosed patients. So very, very exciting to see that earlier use of CAR T-cells.
So this was an abstract from Shanghai in China actually, and it's a single arm study using a dual targeted T-cell. So what this means is that the T-cells had two ways to target the myeloma. So it's not like bispecfic where it was targeting and the myeloma because it is a T-cell. So this is a T-cell that has a double target directly against the myeloma.
So this shows you here the dual targeting. So the BCMA is on the myeloma and then this other target called CD19 is also on the myeloma and is expressed particularly in the early growing myeloma, which what are called the progenitor cells. So it's helpful to get more of the mature myeloma cells as well as the younger actively growing myeloma cells. So this has the option to make this potentially much more important.
What many people were very excited about was the fact that you could take the myeloma cells out of the patient and get that manufacturing to prepare these specific dual targeted T-cells within 22 to 36 hours. Now the comparison is, with the regular BCMA targeted T-cells, it can take several weeks to do this. So this is a huge advantage. When you have to wait several weeks, that means that you need to take what's called bridging therapy while you're waiting, which can get to be rather complicated. In this case, you don't need to do that. So it's a huge advantage. Plus, since you're harvesting the T-cells much earlier in the disease process, they're much better quality and there's a enhanced number of them as well.
So the way that this worked is that patients with newly diagnosed myeloma received two cycles of a standard of care therapy, velcade, revlimid and dex. Then they went ahead and got these what are called the FasT CAR T-cells.
The response, very impressive. What can you say? The first 17 patients' overall response rate, 100%. Just amazing. These patients had a dramatic benefit when CAR T-cells were used in this fashion and the MRD was also 100%. 17 out of 17 had MRD negative and then the traditional response was in excess of 80%. Now with early follow-up, the traditional response takes a little bit longer to clear the myeloma protein out of the bloodstream. So that tends to lag behind a little bit. Very exciting to see this impact using CAR T much earlier in the disease. They decided to start with patients who have high risk myeloma where new therapies are required. So these patients in addition had like 17P minus plasma cell leukemia, extramedullary disease, other kind of high risk features. So quite remarkable to see this kind of benefit.
So I don't know if you guys had a chance to follow up on this. I believe this was presented as a virtual presentation I think. So any thoughts? So maybe Nick, maybe you could comment first. What do you think about this?
Nick Lenoir:
So going through CAR T, I know that time from when you test to collecting yourself to actually going in, it can be quite a long drawn out period. The FasT CAR, I mean, you don't have to do bridge therapy anymore or anything like that. So I think this is all great stuff moving forward.
Dr. Brian Durie:
Absolutely. I see a question there. There was a lot of interest and excitement, when can we get this FasT manufacturing to the US? I don't know about that, but that was one of the questions I was getting. When can we start doing this in the US? So don't know the answer to that yet. So Linda, what was your reaction to this?
Linda Huguelet:
Oh, I agree that I think right now, we've seen people in our support groups getting the two approved CAR T-cell therapies, but many wanting to get them that there aren't slots for them. From what I understand, a lot of that is because of the manufacturing process and the time it takes. So if we could speed up that process, I think that would open up more slots for patients.
Dr. Brian Durie:
Exactly.
Linda Huguelet:
Obviously these results were just outstanding with the upfront patient. We also did hear a discussion about another US based called NEX-T, which was also an attempt to speed up the manufacturing process. So hopefully there'll be a lot of competition for that and bring the best to the market, to the patients.
Dr. Brian Durie:
Right. I see a question here, how long are these responses going to last? So the average follow up on these patients was a bit less than a year. So time will tell what will be the longer term impact. So these are early days and so we don't want to get ahead of ourselves here, but certainly initial results, very promising.
Okay. So changing gears completely, there was tremendous interest in one of the 10 abstracts from Iceland, and it was predicting the need for an upfront bone marrow sampling test in individuals who have MGUS. So what is the story here? So in Iceland, they have been screening the whole population of Iceland over the age of 40 to see if they have a monoclonal protein by electropheresis and actually Mass Spectrometry in the serum.
It's been a huge, huge accrual. Over 75,000 people signed up for this project, so you had to give informed consent for this. So this is the largest study ever done where patients were signed up for informed consent. The reason for that is that they were randomized to get standard of care, which would be to do nothing, or to have a little more intensive guidelines or to really get detailed testing and even to be offered therapy if they happen to have smoldering or active myeloma. So you can see that over 3000 MGUS patients were detected from this method.
So they set up this, it's an artificial intelligence approach to try to understand which of these patients who were screened would have 10% or more plasma cells in the bone marrow. So the reason for that is that if you have less than 10%, then you've got MGUS. If you have more than that, you could have smoldering or even active myeloma. So if it would be predicted that you have less than 10%, then you could hold off on the bone marrow because probably you have MGUS and there's no need to rush in necessarily and do a bone marrow and look for other things to be done.
They picked four predictors to see who needs the bone marrow, the isotype... If you look down at the bottom right of the slide, you'll see predictors says isotype. So that means the type of the MGUS, IgG, IgA or biclonal. M protein, that means the amount of the protein. FLC, that's the free light ratio. Then the total levels of the normal IgG, IgA and IgM.
So those four things, they're all readily available tests. I would have to say it took people's breath away when they said, "Well, what was the correlation with this method?" It shows it, the blue and then the dotted line. The actual and the predicted were almost completely overlapping. So they were able to predict who was going to have an elevated percentage of plasma cells in the bone marrow and those that needed a bone marrow test and those where you could safely wait. Out of this, 366 of the patients were determined that they wouldn't really need to have a bone marrow done. So a big, big savings for the patients and also for costs.
So the Iceland team have put together a risk calculator. So doctors and patients, they just need to load in their numbers and then you'll get your percentage. Then you can decide what you want to do with the information. Now if you're younger and you really want to know, you might want to do the bone marrow anyway. I mean, that's up to you, but if you're frail and old and it's less than 10%, you might want to wait a while. So it gives you that personal flexibility.
So this is an evidence-based approach. It's a shift from the group-based approach that's been used in the past and really could be an amazing way forward. Obviously it does need to be validated by other teams, which I think will happen rather quickly because of the level of excitement about this. So Linda, maybe we'll start with you on this one. So how did this strike you?
Linda Huguelet:
Oh, I think the whole iStop project is so exciting because we all started out as MGUS and smoldering patients. We just didn't know it most of the time. So I think that's just so promising for the future of early detection and then obviously possibly being more curable at that stage. So I was just super excited to see the correlation between the actual and the predicted outcome and how strong that was and how that's moving this project forward.
Dr. Brian Durie:
Thank you. Yeah, and Nick?
Nick Lenoir:
I mean, the iStop is amazing and what they're putting out is great. To be able to have a calculator that you can put information into and then you can, right there, start having that discussion with your doctor or getting the information you need to make your own decisions, that's phenomenal. I hope we can keep moving forward with that type of research because that's what we need, is the information and how we want to be treated.
Dr. Brian Durie:
Absolutely, absolutely. I fully agree that this is not only important in itself for this bone marrow sampling, but also it's kind of a model for the future. I anticipate that there will be calculators for a variety of decision processes. So in a moment, I'm going to show you the results with what we call the cure trials. So I'm sure that we will be able to come up with a calculator that will be able to tell patients, okay, what are the chances that you could be in that group that does really, really well and might be cured and then benefit from treatment that is a little bit more aggressive. So I do see this generally as a way forward. So pretty exciting.
Okay, let's keep moving forward. I selected these six categories, but there were a huge number of abstracts at ASH. So just to be aware, I picked the ones that I thought were the most worthwhile for our joint discussion. So I think that we were all very pleased to see the results of the ASCENT trial. This is a US trial looking at a fixed duration of therapy with daratumumab, carfilzomib, lenalidomide and dex, so a quadruplet, four agents for high-risk smoldering myeloma using the 2-20-20 criteria. So the level of the spike, two grams, free light, 20, plasma cell percentage, 20. So using those criteria to decide to give treatment or not. Fixed duration, two years. So the idea is to have two years of treatment, stop, and see how well you do.
So this is just the 2-20-20. There's also a scoring system with an app actually that you can use. The endpoint was to try to have that best response, stringent CR or MRD negative. So just to give you an idea of the treatment, pretty intensive, four-week cycles with an intensive regimen, then the consolidation and then the maintenance. You'll notice that the daratumumab continues through each of those segments, including in the maintenance out to that two year time point. So the best response, very, very high response rate, 97% of the patients responded. Of those, 84% were MRD negative. So remarkably good results. Again, the traditional response kind of lags behind that a little bit. Also, the achievement of MRD increases over time and not all of the patients have actually completed the whole treatment so far, so that actually the MRD rate could go even higher with this particular protocol.
This just shows you that the outcome is obviously incredibly good. 90% patients doing well out to three years. We obviously need longer follow-up. So this regimen is obviously an aggressive regimen, but it's one that's used for myeloma treatment and we didn't see anything unusual in this particular population. I would say it was a little challenging. This trial was going on during the Covid pandemic. So I would like to congratulate the patients and the investigators for coming through this during that very difficult time. We'll be looking to see if that MRD negativity is sustained and if there can be a fraction of patients who could meet criteria of being cured, which would be obviously tremendous.
Now at the same time, the Cesar trial, very, very similar trial where the patients received KRD and not dara, but an autologous stem cell transplant. So they got the KRD, then they got a transplant and then consolidation and maintenance.
So what was achieved with that, you could see the same kind of thing. Overall response rate, 95%, you can see the greater than CR, which includes MRD negative, 63%. So a little bit lower than what we saw with the dara combo, but really, really good.
So Mary V. Mateos on behalf of the Salamanca Spain group, she showed the length of the remission and the overall survival at 70.1 months. So basically six years. You can see again, tremendously good outcomes at that six year time point. Seven patients have died, only three related to the disease, actually. So we are really optimistic that this will be a way to go. If we can have a way to identify patients who are going to be in the very best groups, that will be even better. So I don't know how these results struck you guys, and maybe Nick you like to comment first about this type of data.
Nick Lenoir:
So the induction, the treatment, and then the maintenance, just looking at the dosing, it was pretty intense treatments, but I mean, that's two years of treatment. To be able to get, what, close to 70 months was what they're looking at right now. I mean, that's phenomenal, phenomenal. I mean, that's why we do this is to try to get more time.
Dr. Brian Durie:
Absolutely, absolutely. I see some comments coming in on the chat room. I mean, obviously these are what are called pilot studies, so they're single arm and we want to see what can be achieved. Obviously for the future, we can slot in maybe some of the exciting bispecifics to make sure that everybody is MRD negative and we can also look at randomized comparisons and things like that. So this is just kind of a starting point. Linda, what did you think?
Linda Huguelet:
Yeah, I was encouraged by... They included basically a duration of therapy and stopped the maintenance after a certain time period, which is certainly a big question for patients with active myeloma or who are being maintained on maintenance drugs. So that was very interesting to me and I think would also make the rigors of the initial therapy more appealing to patients because they feel like maybe there is an end to it.
Dr. Brian Durie:
Right, exactly.
Linda Huguelet:
Perhaps a good way to entice participation in those types of studies and then, in the future, hopefully for non-study patients.
Dr. Brian Durie:
Absolutely. I think that this is a very attractive feature. I actually did a podcast with the very first patient, a gentleman who is the first patient in the ASCENT trial. So right now, he is about four years out, which means that he's been off treatment for two years and he's MRD negative. He's still in a full response. I have to say, he wasn't exactly jumping up and down during the podcast, but he was pretty pleased to be off treatment for two years.
Nick Lenoir:
That would make me happy.
Linda Huguelet:
It would make me very happy.
Dr. Brian Durie:
Right. So I think that this is definitely an attractive feature. We have a lot more information about these patients. FISH testing was performed. I can see that we have genetics, we have all kinds of information about these patients and there will be more to follow. Some of these patients had what you would consider normal things that can happen to myeloma patients. One developed a second cancer, one developed myelodysplastic syndrome, MDS, things like that. So normal things can happen in these kind of trial patients. Yeah.
Okay, so let's move on. So if you are trying to assess how good has the treatment been, then using your best testing for minimal residual disease to see are there any myeloma cells left in the bone marrow or in the blood after you've completed your planned treatment? So this particular study looked at patients who were receiving maintenance in one of the Spanish trials, GEM2014 main trial.
So you can see here, it's a study that compares revlimid and dex and then with the addition of [inaudible 00:40:00] So then looking at the MRD and you can see the red arrows at the different time points, looking at the MRD in that period after the induction. So the important thing from a monitoring standpoint is that they used next generation flow, in this case in the bone marrow. Then they did quantitative Mass Spectrometry, QIP-MS, Mass Spectrometry, which is a very, very sensitive way to measure the level of the myeloma protein in the blood. Then immuno fixation, which is the standard approach to measure the level of the myeloma protein in the blood. You can see that the next generation flow in the bone marrow and the Mass Spectrometry performed much better in terms of the ability to see if any disease was left.
So this clearly was important in determining the outcome of the patients. If you were NGF negative in the bone marrow, you did much better. If you had no spike picked up on Mass Spectrometry, much better. Imuno fixation really was not performing well. It's important to realize that this is what we do right now. Right now, what we do is immuno fixation. So we desperately need to switch to these other new tools, Mass Spectrometry and next generation flow. Fortunately, two commercial companies have bought these methodologies. Becton Dickinson, a large technology company, has bought the NGF method and then the Mass Spectrometry has been available through the binding site. This has also been bought by another large company. So these will move forward to be commercially available hopefully within this upcoming 2023.
Now, the ability to measure using these techniques, particularly with Mass Spec in the blood, allows you to see if the MRD is sustained. If the MRD is sustained, then the patient's going to do even better. You see over to the right here, sustained MRD with both methods, much, much better. So if you can do it simply using a blood test, makes it much better, easier, and it really gives you more guidance as to what's going on.
Now, a lot of interest in looking at the next generation flow test, not in the bone marrow but in the blood. So this is Bruno Paiva's team from University of Pamplona in Spain. He's looking at an ultrasensitive method for trying to identify myeloma cells in the blood.
So we first aimed at investigating the prognostic value of MRD assessment in the blood. Our second aim was to develop a new method with increased sensitivity, so to see if MRD testing in the blood was worthwhile and to make it as sensitive as possible. So this new test, which is called the blood flow test is ultrasensitive because Bruno used magnetic beads to capture the myeloma cells in the blood. So to enrich and purify the myeloma cells allows you to have this ultrasensitive detection. You can see that a particular pattern of antibodies was used for that, but amazing, sensitivity down to 10 to the minus seven, 10 to the minus eight. So that means that you could pick up one out of a hundred million cells. Very, very sensitive.
This means that looking for myeloma in the blood could become a standard of care. This could be a way to look for myeloma in the blood rather than in the bone marrow. This just shows you that this is important. If you're negative using this very, very sensitive method, that's that blue curve. You do really, really well if you are negative at this 10th of the minus seven, 10th of the minus eight level. Then done at the bottom, it kind of shows you the log plot of who's negative and who's positive. So very, very exciting couple of abstracts. So I don't know what your reaction is to having this type of very good sensitive testing in the blood versus the bone marrow. Nick, you want to go first on this?
Nick Lenoir:
I mean, how do you not get behind better results from blood than bone marrow biopsies? I mean, I think anybody's going to line up for the blood test compared to the biopsy. So I love seeing this. I am reading, looking at the slides, everything. This is the next testing and the presentation was phenomenal.
Dr. Brian Durie:
Yes, yes. Linda?
Linda Huguelet:
Yeah, like Nick said, nobody's lining up to get bone marrow biopsies very often, but this also hopefully leads us to the sensitive testing to know maybe when maintenance could be stopped in the future. I guess my question is too, now when we make treatment change decisions, we're making it on less sensitive information. So how do you see that changing, Dr. Durie, as far as do we still wait for some of the typical signs or do you think...
Dr. Brian Durie:
Right, right.
Linda Huguelet:
So we don't jump too soon, I guess, to another treatment.
Dr. Brian Durie:
Right, right. Well, that last point is a very, very good point. I do see our sort of standard recommendations for monitoring and care changing in the next couple of years where we can use these very sensitive tests in the blood to better guide treatment decisions. The one advantage is, in the blood, you can do several tests. So this concept of sustained negative is particularly important, which can be achieved in the blood versus having to do multiple bone marrows. So I do believe, and through our international myeloma working group, we're going to be looking at different protocols which incorporate these types of analysis so that we can come up with new guidance, new standard of care consensus recommendations. So things will be changing and changing for the better, not just because we have the testing, but also because, with the bispecifics, with the CAR T, with all these new therapies, we'll have a lot more patients who are at that MRD low level and where we will need these tools to see what we're achieving.
Okay. How soon are they thinking the new blood testing will be available in the US? Well, as I said, Becton Dickinson bought the NGF method. They're going to be rolling it out in this next year, so I think fairly soon.
Okay, so changing gears again, dexamethasone sparing. So obviously dexamethasone is the drug that myeloma patients love to hate. It can really do a number and if we can get away from it, that's certainly one way to try to move forward. So this was an interesting French study, IFM2017-03 trial, where they looked at a combo without dexamethasone. Now there has been tremendous excitement these last 3, 4, 5 years about what's called the Mya regimen, which is daratumumab, lenalidomide, plus dexamethasone. So basically what this study did is it took the Mya regimen, but it cut out the dex.
Then they compared it to... Unfortunately they compared it to lenalidomide dex. They didn't actually compare it to the full Mya regimen, so you don't have a direct comparison, actually. What they did do is, you can see here, they compared len and lo-dex with len plus the dara. Then they looked at the side effects and the outcomes. So obviously, the len plus the dara subQ was pretty well tolerated, although there are definite side effects with both len and Dara, actually. We're focused on the decks, but the len and the dara can sometimes be no walk on the park either. So we need to pay attention to that. Here, you can see that the best response with the dara-rev at 96%, 85% with the rev-dex.
The main thing I'd emphasize here is if you look over to the right MRD at 10 to the minus five, it was 10% and 3%. These numbers are not nearly as good as those achieved with the full Mya regimen, with the dexamethasone. So on the plus side, you don't have the dex side effects. On the negative side, you maybe are not getting quite as deep a response.
So a lot of positive excitement about this, particularly for frail patients. Safety, very good. I think there was a lot of interest in the last arrow here on the bottom of the slide. The PFS analysis is ongoing. The responses were pretty good, but we need to see how long are the responses lasting and what is the true differential in terms of benefit by dropping the dex. Maybe there's a compromise where you could just have a low lo-dex, some sort of dex that maybe could give you efficacy and be tolerable. So anyway, what did you guys think about this? No, dex.
Nick Lenoir:
Down with dex. Yeah.
Dr. Brian Durie:
Down with dex. So Linda, what did you think?
Linda Huguelet:
Yeah, I agree. I mean, dex can be... For me, I'm particularly sensitive to it. So even at a very low dose, I don't sleep. I don't have a lot of the other side effects, but I don't sleep. I found in my group, the patients that I would consider frail in this category, they do, like you mentioned, have more issues with the actual regimen and not the dex. It's great that they're talking about it, but I think there is a lot more work to be done, I think, on whether we eliminate dex or, like you say, maybe we just lower it to a greater degree. I know there was a lot of action on Twitter during the conference about down with dex and even for other regimens. It is something that sometimes you wish your doctor took the dex and could really understand what it's like to be on it. So certainly I'm glad they're starting to look that way. I'm not sure that we're there yet.
Dr. Brian Durie:
Right, right. No, I agree. As you can tell from the way I was introducing it, I feel at least, we shouldn't just completely throw away the dex. So there was obviously a crucial study, which was the four days of dex, the high dex versus the low dex, the one day a week. I think that that was crucial because we know that the one day a week of dex can work, but even with that, that one day a week is 40 milligrams. So there's quite a bit of flexibility. In fact, most doctors don't even give that 40 milligrams to frail patients. They would start even with 20 milligrams. So you have some flexibility to come down from 20 milligrams to lower doses or even eight milligrams or so.
We do know that having some dex has an advantage over no dex. So I think that we don't necessarily need to rush away from dex, but maybe individualize it. Some patients do not tolerate dex well. Others kind of like it. They take it on the weekends and get a bit of a boost and they're not so upset about it. So anyway, I would recommend a flexible approach to this information. So Nick, would you support that idea?
Nick Lenoir:
I do see a need for dex. I have people in my group that have been on just revlimid. They started seeing their numbers creep up, they treat it with a little bit of dex with their revlimid, and they've started getting it back under control. Now, do they have to stay on dex or can they keep on their... So these are all questions that are now being had. I mean, yes, Twitter was abuzz, the whole place was abuzz. People were talking about, do we need dex and how long? So I mean, the conversations are being had and I'm thankful for that. Some people need it, some don't.
Dr. Brian Durie:
Right, right. So thank you for that. So what I'm watching is the questions coming in on the chat box. I can touch on some, and Robin, if you're still there, you could maybe draw my attention to some that could be important. One, which I see here is number 53, which is more toxic len-dex versus low doses of the bispecifics.
I think that the one thing we didn't really talk about with the bispecifics is that eculizumab, the BCMA bispecfic, which is approved by the FDA, and we're just starting to get a handle on in the clinical setting, it's given on an ongoing basis. One of the concerns that we touched on is that there can be infections, like pneumonia and other side effects. So what we need there is to think about what we were talking about with other therapies, maybe a fixed duration with the bispecifics where you maybe take it for a year or whatever and then try to avoid some of the other side effects. Overall, I would say that len-dex is pretty well tolerated. We do need to look at the toxicities and side issues with the bispecifics. You have that step up dozing, so for the first week or two, the patient does need to go into the hospital for that. So the bispecifics are tremendous, but there are some things to think about.
Robin:
Dr. Durie, maybe you want to look at number 49. Are we getting any [inaudible 00:56:41]
Dr. Brian Durie:
Can we scroll up to that one, 49? Let's see.
Robin:
So it's about stem cell transplant. So thinking about using, since all of these other drugs in that relapsed refractory setting are showing such amazing results...
Dr. Brian Durie:
Right. Oh yeah.
Robin:
We know that there are some of these things being studied upfront. So there's a little discussion here about the using stem cell transplant.
Dr. Brian Durie:
Right. Absolutely. I do think that this is a very, very reasonable discussion. I think that it's been sort of heightened by the data coming out of the IFM study and the determination trial, which was VRD plus or minus autologous stem cell transplant. So the remission was prolonged, but the overall survival was not enhanced with the incorporation of the stem cell transplant.
So this has raised this question about who should be transplanted and what is the full impact of a transplant. It seems to be mostly, if you can achieve that MRD negative, so if you get the transplant, you get more patients that become MRD negative. So if you look at it in that way, it's quite likely, in my mind, that you could get a whole lot more MRD negative with CAR T versus a traditional stem cell transplant. So that's why for me, the results of that dual targeted CAR T frontline from China was very, very intriguing because it was sort of pointing the way forward. The Chinese actually have been kind of the pioneers and the leaders in this CAR T. So I do think that that could be the way forward. Also this kind of one and done approach, it kind of gets away from ongoing toxicities with infections and other kinds of issues. As I was saying earlier, it's great to be off treatment. If you're MRD negative and you're off treatment, this is very, very good.
Okay, so maybe you have time for one last question. Anything catch your attention, Robin?
Robin:
A lot on revlimid and maintenance. It's nice to see that there are studies now out there and there was one, Dr. Durie, looking at... Was it 2, 3, 5 years?
Dr. Brian Durie:
Yeah. Of maintenance, yeah, yeah. My own feeling is that if we can have a fixed duration of therapy, including the maintenance with traditional regimens, I mean, that would be ideal if we could achieve that. Yeah.
Robin:
I think that the study didn't show... It needed longer time. I don't think it showed that, at this point, we can make that decision.
Dr. Brian Durie:
Exactly, exactly, but maybe with the MRD testing, with sustained MRD negative, we would have a comfort level to go ahead and stop. Yeah. So anyway, I think that we have reached the witching hour here, and so maybe I can ask our panelist. I'm very, very grateful to you for your feedback from the patient perspective. Maybe you could comment on just what it was like to be at ASH and then any other final words of wisdom for our listeners. Linda?
Linda Huguelet:
Well, I mean, ASH always ends my year on just such a high note because the amount of research that's going on and just the dedication of all the scientists looking, not only for new treatments but for a cure, is just amazing and really overwhelming. I would hope that everybody listening tonight would also check out the blogs that all the support group leaders wrote. A lot of different perspectives, as Nick mentioned, a couple of nurses in our group, some who are smoldering, some who are more veteran patients like me. So a lot of really good information and food for thought in those blogs. Of course your final ASH blog is terrific as well. Thanks for the opportunity to participate.
Dr. Brian Durie:
Thank you so much. Nick, some final thoughts?
Nick Lenoir:
Just the whole experience to see what is actually going on out there in the research world. I mean, as a patient, I've been on multiple clinical trials myself. You only see what you're doing. You don't know what's going on out there in the world. To be able to go there and see all the different advancements they're trying to make for us as patients, I hope I can go every year from now on and just see how next year's going to build off of this year with the MRD testing and Mass Spec. I mean, where we're going next is really giving me hope in fighting this.
Dr. Brian Durie:
Great, great. Thank you for that. Yeah, so thank you to both of you and to Robin. Again, we obviously always thank our sponsors and really grateful that they appreciate the value of this type of information sharing. So for those of you who are with us here, we are interested in your feedback as well. So this just tells you how to click and give us a little bit of feedback about the webinar. It's a short survey and so we will really appreciate that. So good day, good evening from the International Myeloma Foundation. We appreciate the chance to share this type of information with you and obviously we are wishing everyone the very, very best for the holidays. I hope everyone can have a chance to have a little bit of a break and have a careful time with your family and friends. So thank you all. Have a good evening.
