Best of 2022 ASCO & EHA Webinar

What’s New in Myeloma Research?

IMF Chairman Dr. Brian G.M. Durie discusses some important new findings from the 2021 American Society of Clinical Oncology (ASCO) annual meeting that took place virtually from June 4-8 this year, and from the subsequent European Hematology Association’s (EHA) annual meeting. He highlights scientific abstracts from these meetings that discuss the following topics:


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  • Immune therapies, including CAR T-cell therapies and bispecifics
  • Four-drug combinations, including those that add daratumumab to current three-drug regimens
  • Treatment of high-risk disease
  • The benefits of whole-body MRI versus PET/CT scans in baseline imaging studies
  • The emerging role of mass spectrometry for low-level disease monitoring

Dr. Durie explains this data in approachable terms that patients and caregivers can use in their everyday care decision-making. 

The webinar concludes with a summary discussion and closing remarks.

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Robin Tuohy: 

Welcome everyone, and thank you for joining us for the International Myeloma Foundation's Best of ASCO and EHA 2022 Webinar, What Patients and Care Partners Need to Know. I'm Robin Tuohy, Vice President, Support Groups. Tonight, Dr. Brian Durie will discuss some important new findings from ASCO, which is the American Society of Clinical Oncology annual meeting that took place in June and also from the subsequent EHA annual meeting, which is the European Hematology Association. Dr. Durie will highlight scientific abstracts on immune therapies, drug combinations, treatment of high-risk myeloma, and so much more. You'll note that Dr. Durie will give his famous bottom line and will also include the link to the principal investigators' more detailed summary of the abstract, which will also be patient and care partner-friendly and easy to understand. 

So before we get started and on behalf of the IMF, I'd like to thank our sponsors for supporting this educational program. They are Bristol Myers Squibb, GSK, Janssen Oncology, Karyopharm Therapeutics, and Sanofi. A few items for housekeeping. So you can participate during the open Q&A at the end of our call. Here are some instructions on how to send us your questions. Dr. Durie will address as many questions as possible tonight, but please remember that if your question does not get answered today, that you can contact the IMF info line. If you have a technical issue that arises, you can also let us know, and we can assist you. On this slide, it tells you here's how to do that. Next slide, please. 

Your feedback is important to us, and we want to hear from you so we can continue to provide you with the information you need to provide you programs of most value. We kindly ask you to take a moment at the end of our webinar tonight to complete that survey. As always, a replay of this webinar will be available on the IMF website early next week, so let's get started. It's now my pleasure to turn this over to Dr. Brian Durie, IMF Chairman of the Board, Chief Scientific Officer, Professor of Medicine and hematologist/oncologist. Dr. Durie, would you please begin? 

Dr. Brian G.M. Durie: 

Well, thank you so much, Robin, for that great introduction and explanations of how things will go today. So welcome everyone to hear about what happened at ASCO and EHA this year. It was pretty active, and for the first time, both meetings were a combination of in-person and online, what are now called the so-called hybrid meetings. If we have Slide #3, which I hope that you have in front of you now, Slide #3 provides the initial summary of what happened at ASCO, which as Robin said, was held in Chicago this year. There were over 5,000 total abstracts submitted this year of which 168 related to myeloma. We were very fortunate this year that a plenary abstract was about myeloma, which is pretty rare, so we were very fortunate to have a special abstract on myeloma, which will in fact be the first abstract that I talk about. 

There were 13 oral presentations and a number of posters for discussion and just submitted. Just to comment about all these different abstracts, we only touch on a few, which tend to be larger multi-institutional trials and studies which we rely on for scientific data. Many other abstracts often report data from single institutions. Just to say that this is also important. For patients, it's actually very important to know. "Well, what is happening with new treatments when they're being used at my local center?" So a number of these abstracts are actually quite important, although we tend to not emphasize them when we're giving these broad discussions.  

So if we move to the first abstract, which is the one that was the plenary session at ASCO, so a very important abstract presented by Dr. Paul Richardson from the Dana-Farber. This is the first time to have a major presentation about this particular trial, which is the combination of lenalidomide, bortezomib, and dexamethasone (RVd) with or without autologous stem cell transplant, and all patients did receive lenalidomide/Revlimid as a maintenance. This is a follow-on to a similar study that was conducted by the French, the IFM 2009 trial in which the results have been presented and published actually, so I'll comment on that as we go through. The difference is that in the French study, the lenalidomide maintenance was limited to one year.  

In this particular trial, so there were 722 patients who were randomized. Half were randomized to receive the collection of the stem cell but did not get the high-dose melphalan as a stem cell transplant, and that is the light blue on the top of this particular slide. Then on the bottom, the pinkish color, you can see that they did have stem cell collection followed by the high-dose melphalan, 200 milligrams per meter squared, followed by consolidation with another four or five cycles with the (RVd) before going on to the Revlimid maintenance, so very, very similar to the previous French trial.  

The key findings, again, similar to the French study, if you look here at the bars on the right of this chart here, you have the orange, which is the patients who received ASCT, which is autologous stem cell transplant, and then the blue, which is the patients who did not. They received the (RVd) alone. You can see the three types of charts, so on the top, it shows you how many patients were still in remission after five years. You can see the ones that got the stem cell, 55.6% were still in remission at five years versus 41.5% without the stem cell transplant. 

Basically, this translated into a longer first remission for the patients receiving transplant of a little bit over a year. Down in the white box on the bottom left, you'll see that that length of first remission was 56.4 months for the patients with the transplant versus 38.9 months for those not receiving the transplant, so remissions lasted over a year longer in patients receiving the transplant. What has really caused a lot of discussion and comment is the middle set of bars, and you can see this represents the Overall Survival. You can see the Overall Survival at five years was 80% versus 79%, so really no difference, so the question is what is going on here? There are lots of different discussion points. I think in this case, it is quite helpful to think about listening to the interview with Paul Richardson because he discusses all of the different issues. Well, is it because of this? Is it because of that?  

One of the main things is that obviously, if you did not get the transplant, a percentage of the patients did go ahead and get the delayed transplant. That number was 28% actually. 28% were able to go ahead and get the delayed transplant, but the thing about it is that they were able to go ahead and get all kinds of other backup therapies, including the exciting new immune therapies that we're going to be talking about today. So, there are a lot of opportunities to recoup that survival, even if you might relapse a bit sooner without the transplant, so the discussion goes back and forth then. Should patients go ahead and get an autologous stem cell transplant? I think that most investigators still answer that question, "Yes, because it does produce good quality first remissions, and it does last over a year longer."  

I think an important point from the patient perspective is that it doesn't close any doors. I mean, if you've had the transplant, but you could still go ahead and get those exact same exciting new immune therapies after that, just the same as the other patients. It doesn't close any doors, so if it's feasible, I think that most doctors are still discussing that option with the patients. If you want to hear the direct scoop, please listen to the interview with Dr. Richardson. 

Okay, so a second abstract that was prominent at the ASCO meeting this year is the one highlighted here, actually from Monash University in Melbourne, Australia, which is a research team that works with the Black Swan Research Initiative, IMF Black Swan Research Initiative. This particular abstract was in the ASCO newsletter. During ASCO every day, there's a newsletter that comes out highlighting what ASCO thinks are some of the most interesting abstracts to be presented that day, so this particular abstract was selected as one of the most interesting papers of the day. The reason for that is that it looks at a completely new way of understanding why patients are resistant to therapy. What this team has done is looked at the DNA which gets released into the bloodstream circulating tumor, so CT, circulating tumor DNA, and in this case, obviously the tumor is myeloma. As the myeloma is growing, it does release some DNA into the blood. The more myeloma and the more active the myeloma, more DNA comes into the bloodstream, so this can be used to assess what's going on.  

This is the full abstract that was presented, but the main point I would like to emphasize is in the middle part of the slide here where it says circulating DNA analyses identified actionable mutations in treatment-resistant multiple myeloma patients. So in the patients who were failing on this particular protocol, which consisted of Kyprolis, thalidomide and Dex ... Thalidomide tends to be used outside of the US instead of Revlimid. Anyway, the patients who were not responding to that or relapsing early within a year or so, they had more of this DNA in their blood, and they also had these particular mutations. 

The ones that were drawn attention to are RAS and RAF, R-A-S and R-A-F oncogene mutations. This is quite important because these are mutations which occur in other kinds of cancer such as lung cancer, so we do have treatments for that. What the Australian team is doing now is for those patients with these RAS and RAF mutations, they have trials where we can use these completely new types of treatment to attack these mutations that they have found in the blood and with some success in individual patients. Larger trials are ongoing. 

Okay, so I think everyone knows who's been watching the myeloma landscape these last few years is that the introduction of bispecific monoclonal antibodies and the CAR T-cell therapies have really had the biggest impact in terms of new potential approaches to treatment, so there were quite a number of abstracts presented on those two types of immune therapies, and I'm going to start with the bispecifics.  

This first couple of abstracts here dealt with teclistamab, which is a bispecific antibody, and bispecific means that there are two arms to the antibody. One attaches to the myeloma through the BCMA and the other arm attaches to the T-cell through the T-cell receptor, which is called CD3. So, you have these two arms, one to the myeloma and one to the T-cell to bring them together and to increase the attack against the myeloma. Now teclistamab has been in trials for a number of years now, and the data have been submitted to the FDA. In fact, there is what's called a PDUFA date where we actually expect to hear from the FDA sometime in August if they will go ahead and approve this particular bispecific, teclistamab.  

Over on the left of this slide, we have an update of the data that's been submitted to the FDA, the Overall Response Rate, 64%. As Robin mentioned, I put the bottom line information in red here. Overall Response Rate, 64%, ORR. What was emphasized with this longer follow-up was that the responses are deep and durable, so really quite encouraging data. What we have over on the right, and this is a theme as we go through a number of these other abstracts is that teclistamab is being evaluated in combination with actually a variety of things but in this case, daratumumab, which is also a product produced by Janssen, so it's very easy for them to combine two products that they produce. This is early data. Bottom line, it is possible to potentially get enhanced activity, and it's tolerable to give the two agents together, so encouraging early data, really.  

Additional data, and you'll see this. Similar data tended to be presented at ASCO and EHA, so just for completeness, I'm bringing it together here. The data were presented by Niels van de Donk at EHA. The other thing that was important that was presented at EHA was looking at how well does teclistamab work, and this is over on the right presented by Cyrille Touzeau. Again, you could listen to his interview. How well does it work in patients who have previously received some other therapy that targets the same BCMA on the surface of the myeloma? This would be obviously something like the ADC that we're going to be talking in a little bit, another type of BCMA therapy. 

Now, something that's quite interesting is teclistamab is obviously being offered in the relapsed/refractory space, so it was interesting to see, okay, how well does teclistamab work versus if a patient was to receive selinexor and dexamethasone, sel-dex? The answer to that question presented by Dr. Bahlis was that the teclistamab performed really quite well, equally well, maybe even marginally better versus selinexor-dex in that similar matched population. These are the sorts of things that you see quite a bit of now where we're trying to match and see, without actually doing a trial, if one treatment might be equivalent to or maybe even slightly better than another one in the same type of relapsed/refractory patient. 

So, teclistamab is one bispecific which is likely headed for FDA approval, but there are a number of others. Two were actually presented, one at ASCO and the other at EHA. This is the first one from Pfizer, elranatamab, another BCMA bispecific. This was being tested in patients who had not had any prior BCMA-directed therapy. This was an early study but with really quite promising results. They were testing the dosing and what they call a step-up priming. The idea with the bispecifics is to have benefit but to reduce early toxicity. We're particularly concerned about CRS, cytokine release syndrome, which can happen if the bispecific has a very dramatic initial benefit. They had a two-step priming dose with 76 milligrams, and that seemed to work out very well in terms of both tolerability and as well as efficacy, so really quite promising results with this new Pfizer bispecific.  

Then this one was presented at EHA. I thought it was just good to go ahead and just show you this one. This is from the Regeneron company, Regeneron 5458, another bispecific. This is not usually what is recommended, but actually the full results of this particular abstract are presented in the title. Normally, you put that in the conclusions, but anyway, be that as it may, in the title, as you can read right here, early, deep and durable responses and low rates of CRS occurred with Regeneron 5458. So in this Phase 1/2 first-in-human study, really excellent results and excellent tolerability. These are the things that are going to be important as we look at several products in the marketplace likely with similar targets. This is similar to where for proteasome inhibitors, we have Velcade, we have Kyprolis, we have Ninlaro, so we have three different products all targeting proteasome inhibition. For anti-CD38, we have daratumumab and then we have isatuximab, so we have two there. I think we're going to see the same for BCMA-targeted bispecifics. 

If the bispecific has been targeting BCMA or other therapies have, what about looking at other targets in patients who are refractory or need additional or alternate therapy? So, a lot of interest in this other first-in-class bispecific talquetamab and in two different trials. See how they pick these amazing names? MonumenTAL talquetamab and then TRIMM-2. These are looking at patients, as I put here on the left, prior anti-BCMA therapy, so we're looking to see, okay, prior BCMA therapy. If you target another target, in this case, this GPRC5D, does this work? The answer to that is yes and was used safely. The same theme is being picked up here. You'll see over on the right, Niels van de Donk is saying, okay, not only does it work, but you can also combine it in this case with daratumumab. So people are really looking ahead into that backup space, single agent and combination, so really quite encouraging early data. 

If we shift from the bispecifics, which is obviously a very, very active part of the myeloma's landscape and look at the CAR-T landscape where the T-cells are engineered, so T-cells are harvested from the patient, sent off to the manufacturing facility and are engineered to target whatever you want. The initial ones are targeting BCMA, so targeting that exact same B-cell surface antigen that we've been talking about. Again, in this case, Carvykti, this is an FDA-approved CAR-T product. It was approved based upon the results of the CARTITUDE-1 trial for the trade name which is Carvykti, cilta-cel. Saad Usmani, I know from Sloan Kettering in New York, updated indicating the very, very high continued response rate with cilta-cel, 98% Overall Response Rate with deep and durable responses continuing because they have follow-up out beyond two years, so very encouraging results with the cilta-cel. 

Then the cilta-cel is also being tested in a variety of additional trials at ASCO and EHA. There was the CARTITUDE-2 where the cilta-cel is being used in patients with earlier disease, one to three prior lines of therapy. This again, as you might imagine, is working extremely well. How much better in the earlier disease states, it'll take time for us to know but obviously working well and is being tolerated well. So what about the other CAR-T product? 

Well, actually prior to the approval of cilta-cel, the ide-cel, the trade name Abecma, was approved, and this was based upon a trial, the KarMMa trial in this case. Interesting in this case, in the KarMMa trial that was submitted to the FDA for approval, the Overall Response Rate was actually 73%, so 73% of the patients had overall response. Now, in this case, Doris Hansen from Lee Moffitt in Florida presented what is happening since Abecma has been FDA approved. What is the real-world experience with this product? Now, the real-world experience unfortunately has been that it's been hard to get the CAR T-cells. I know it's been very frustrating for many patients where it's been hard to get access to the CAR-T, but the interesting thing is that results have been quite good. The Overall Response Rate in the real-world experience was actually 83%, so maybe a little bit better. Obviously the patient population, perhaps not exactly the same patients who are getting in to the treatment, and the real-world setting not quite the same as those who went into that initial trial. 

Just like the bispecifics and actually even moreso, there are a lot of other CAR-T trials. These ones are focused on the BCMA target again. The one from China, which is on the left, presented by Juan Du from Shanghai, really excellent results with a new dual-targeted CAR-T. This is actually quite similar to the cilta-cel, the CARTITUDE type product, very good results. These have been continuing in China despite the COVID crisis. In fact, three years ago, I visited the manufacturing site outside Shanghai where these are processed and produced. They have an amazing facility for producing these CAR T-cells.  

Who knows what's going to be happening related to China, but at that time, it costs the equivalent of about 10 million dollars to build a manufacturing plant. Then in China, it costs approximately $30,000 to produce CAR T-cells for one patient. So, since other therapies, all of the biologic therapies, daratumumab and all of the other different therapies, carfilzomib and the like and Revlimid, these are very, very expensive in China, so CAR T-cells potentially can be more usable in China. In fact, Juan Du is exploring the use of CAR T-cells in earlier disease and even in high-risk smoldering myeloma to see if you use this really early, what can be the benefit. Over on the right, we have some early data from a novel synthetic domain, a slightly different engineered type of CAR T-cells, also against BCMA, promising early data with high VGPR and CR rates.  

So one of the questions that comes up is, "Okay, so maybe you can't get access to CAR T-cells, or maybe you can't get into a bispecific trial. What are the options in terms of combinations of agents that we already have that would be useful?" There were some interesting results presented this year, so I just want to share this one, which really caught my attention, presented at ASCO by Dr. Andrew Yee from Mass General in Boston. He evaluated the response rate and outcomes with the combination of daratumumab combined with carfilzomib, pomalidomide and Dex, so a four-drug regimen and really quite remarkably good results. 95% Overall Response Rate, and it was really quite well-tolerated in refractory myeloma. This really is a combination to keep your eye on as an option if you can't get those exciting new immune therapies. Maybe this could be a tolerable and really quite effective, active combination. 

There was also data looking at pomalidomide, bortezomib, Velcade, and dexamethasone in patients previously receiving just lenalidomide, the OPTIMISMM trial, again, with quite promising results. So pomalidomide in different settings, in different combinations can be used. In this case, they looked at patients who had a high frailty score, so patients who were older and had a number of medical issues. It was quite tolerable for that patient population.  

Another type of thing that is always being looked at is what are the different risk factors that we need to pay attention to that would influence whether a patient does well or maybe not so well. The ones that we've looked at over many years include the (4;14) translocation, and this is a type of genetic change which shows up on bone marrow FISH testing. So if you have a bone marrow test done and it's sent off to the lab, fluorescent in situ hybridization, FISH, can show if you have a (4;14) translocation.  

Now we've known for a number of years that this is a poorer risk subgroup. However, we've also learned in the last five, 10 years, if you give proteasome inhibitors, Velcade, Kyprolis, Ninlaro, if you give the proteasome inhibitors that can improve the outcomes for patients who have the (4;14). This particular study continued to show that in terms of improved outcomes with long-term survival. However, some patients in addition to the (4;14) also have 1q plus or 17p minus, and those poorer risk abnormalities still confer a more negative outcome, so proteasome inhibitors don't overcome if you have these added poorer risk features. 

What about with the (11;14) translocation? This is another one that shows up with FISH testing, and you may have heard about that. Overall, it's been considered to be rather a good risk feature, in the standard risk patient, maybe even a little bit better than average. Well, this follow-up shows that it's maybe a little bit less than the average. It confers a slightly negative risk in patients receiving a three-drug combination, so maybe not quite as good as we'd been thinking in years past. It really does raise the option to think about using the drug, which is called venetoclax, which has been in trials and is actually approved for treatment of lymphomas and leukemias to try to have a better benefit in patients with the (11;14) translocation. 

Then this is something just to be aware of. We use increased serum-free light, FLC, the free light ratio as an indicator of more active disease. In fact, a free light ratio over 100 abnormal over normal indicates that you might fall into this SLiM-CRAB group where it contributes to the idea that maybe you do have more active myeloma. This particular study from Mount Sinai in New York indicates that if you just have an increase in the free light, that doesn't always indicate immediate aggressive myeloma. So, it recommends looking at patients with just elevated free light on a more individual basis if the other testing does not indicate more active disease because some patients with a high free light can actually do well for a number of years. It may be related to the molecular features where it's not excreted so quickly by the kidneys. It's not entirely clear, but just to be aware of that. Just have a little bit of caution if an elevated free light is the only abnormal testing. 

Okay, so let's move on just to finish up what happened in addition at the European Hematology Association meeting. Again, a hybrid meeting. This was held in Vienna. You can see not as many abstracts submitted to EHA versus ASCO. Myeloma abstracts, though, 332. Quite a lot of abstracts looking at a whole range of different aspects of myeloma. I can only touch on a few of them. One was presented at the Presidential Symposium, quite important. Obviously, the DETERMINATION trial was also presented, and then we had oral abstracts and some that were just for poster presentation or publication only.  

The Presidential Symposium, and this is something that I've touched on already. This was about a CAR T-cell therapy that is being developed by the team at the University Hospital in Barcelona, Spain, by the academic group there, so they are developing their own CAR-T therapy. This is an increasing trend. I commented on the CAR T-cell therapy that was developed in Shanghai, China. Then in the US, different groups are looking at producing their own CAR T-cell therapies, to set up that engineering process on site. For example, UCSF in San Francisco, they're looking to start doing that. 

In this case, this was a new type that they had developed themselves, and it was called fractionated, which means that they tried to reduce the CRS by giving it in a fractionated dose schedule, then with a booster, so a new product but also a slightly different way of giving the product.  

The presentation had a very, very nice summary of all of these different kinds of therapies I've been talking about, so I thought it might be nice for you to have this image. Just to be aware of, in terms of attacking the myeloma, you have the CAR T-cells, which can directly attack the myeloma. You have the monoclonals, which can directly attack, and then over on the right, you can have these bispecifics or bispecific T-cell engagers. You can see the slightly different constructs but involving the T-cells in attacking the myeloma. Then obviously there are vaccine approaches, checkpoint inhibitors, different ways of attacking the myeloma. 

Then as far as the engineering process itself, what is called the active head, the BCMA, which attaches to the myeloma can be in different forms. So in the ide-cel product, it's a mouse that's a murine anti-BCMA. In this new academic type, it was a humanized. Then in the cilta-cel it's yet a slightly different double-headed BCMA. There's all kinds of variations in terms of having different. They're just highlighting the one that they had used.  

Again, producing quite good results with minimal residual disease improving, doing quite well over time. Then just showing that their initial results here, 92% Progression-Free Survival. I would say that maybe not quite as good as we've seen with some of the other products I've just showed you. PFS and Overall Survival, 53%, 18 months, so maybe not quite as good as some of the products that I've shown you, but obviously quite excellent data, so we're going to see quite a bit of this, people trying to come up with their own CAR-T therapies and evaluate how effective they are and the like. 73% at 18 months. Okay.  

So, what other things beyond the immune therapies were presented at EHA? I thought that this was quite important. We're always looking at Revlimid maintenance as the standard of care. In this case, Dr. Dytfeld from Poznań in Poland, he presented data showing that if you use Kyprolis, carfilzomib, along with Revlimid and Dex versus Revlimid alone, then you got superior outcomes with (KRd) superior. Then also it produced more MRD negative, 47% versus 29%, so indications that maybe something beyond Revlimid can produce some improved results, so definitely something to think about, particularly if a patient is remaining MRD positive, for example. 

Then I already mentioned the combination from Boston, which was daratumumab plus Kyprolis/pomalidomide and Dex, which had a very high response rate in patients with relapsed disease. There was also a study looking at Dara combined with (KRd) in patients with frontline therapy in the high-risk setting, again with very good preliminary results. Actually, what crossed my mind is that the results with Kyprolis/pomalidomide and Dex were so good, that might even be superior in this high-risk group of patients where we're looking to have as good results as we can, but very, very interesting results, (KRd) plus Dara. 

Then moving along here, there was a follow-up presentation TAK-573. I'll stick with the acronym on this one, a first-in-class, an immunocytokine, so it's a different kind of an agent. It delivers interferon directly to CD38 positive cells. This has been presented in the past, as I said, and again, follow-up data looking at the clinical pharmacology and the immunogenicity, basically promising data that this may be a new class of immune cytokine that maybe can give us some added benefit, so something to be aware of, something to watch for, presented by Dr. Kaufman from Emory in Atlanta. 

Now I'm just going to show you quickly a number of abstracts looking at follow-up data related to Blenrep, belantamab mafodotin. This is what's called a drug conjugate, ADC, antibody drug conjugate. Again, in this case, there was an intent to look at trying to enhance the efficacy by enhancing the expression of the BCMA, the DREAMM-5 study, again quite well-tolerated and quite effective, so good preliminary rate results presented by Sagar Lonial. 

Then a similar trend to what we've seen with other agents looking at the data used in combination with Len and Dex, so in newly-diagnosed myeloma. Thinking about, okay, if we combine this Bela with Rev/Dex, could this be an effective schedule? Initial data are promising there. Then another type of study, trying to match to see how the ide-cel would compare and quite promising comparison between the two. As I showed you earlier, this is the type of thing that you can do. Looking at in this case health-related quality of life, you can compare without actually doing the study by matching the patients. 

Now, another study, just a follow-up. This is a study that we've talked about for the last two or three years in the frontline setting is the GRIFFIN trial. Dara combined with Velcade, Revlimid and Dex. Again, very promising results, trying to validate potentially the standard of care in the frontline setting. Should we use Dara/VRd versus just VRd? Well, in this, what they call post-hoc analysis, they were looking at how sustained was the MRD. The answer to that was really pretty good. The patients who got the Dara had more sustained minimal residual disease, so MRD negative 53.7% versus 20.3%. So it really gives you the idea that this really could be a valid standard of care option, four drugs versus three drugs, so we're still looking for that full study to validate that. 

Another study, just looking at ixazomib plus Dara, showing that this is really quite a good combination. Again, the sort of combination that maybe could work well in elderly and frail relapsing patients. The French have had a particular interest in this in focusing on what works well for these older, more frail patients.  

Then finally, the trend is complete here where isatuximab, that is the alternate to daratumumab, so this is the anti-CD38 monoclonal antibody. As you probably know, daratumumab started off as intravenous and then is now available by SubQ injection. In this case here, isatuximab was given by subcutaneous administration with an on-body delivery system. With interim results, which are really quite promising with excellent efficacy and excellent tolerability, so isatuximab moving forward towards a SubQ administration option, so something as I say, to keep an eye on.  

All right, so I've covered a wide range of things from the DETERMINATION trial, a lot of details about immunotherapy bispecifics, CAR T-cells, and then a lot of information about some of the therapies that we've been using for a number of years, new combinations, new ways of looking at things. We have plenty of time for questions. I believe that Robin is going to try to help me guide through what I can see is quite a number of questions that have been coming in here. Robin, maybe between the two of us, we can try to touch on some of these. 

Robin Tuohy: 

Yeah, sure. Absolutely, and you're right. There's lots of great questions coming in. For those that may have forgotten, there was a slide up there that shows you how to get that Q&A in. I do see, Dr. Durie, in the beginning of your presentation, you talked about the DETERMINATION study, so the delayed versus early transplant with Revlimid maintenance, and then the anti-myeloma triple therapy. 

Dr. Brian G.M. Durie: 

Right. 

Robin Tuohy: 

I know that Dr. Richardson gives a really good interview on that, people could reference, but there are some questions about when should I? Should I? Are there some guidelines for this? 

Dr. Brian G.M. Durie: 

Right, and I think that we're waiting on that, so let me answer that in two parts. I think that one idea is that it should be possible to try to sort out are there some patients where we would say, "Look, in this case, we really do recommend the stem cell transplant. In this case, that's what the patient needs to achieve that MRD negative," because more patients do get MRD negative with the transplant versus not, so if we could sort out which patients are the ones that need the transplant to get that MRD negative, that would help us. Short of that, I think the main thing that everyone is saying right now, on the expert doctor side, is that it really emphasizes the need to talk to your doctor and balance in your case. There are those patients who say, "Look. This gives me a longer remission. I'm young. I'm healthy. Let's do it," and there's that attitude.  

Then there's the patient who says, "Well, it doesn't improve the survival. I do have some medical complications. I'm a little bit older. I don't really like the idea of having this autologous stem cell transplant. It looks like I could skip it for now, and let's just harvest the stem cells and wait." These are decisions between you and your doctor. I think that this has really gone very solidly into this category of, "Talk to your doctor about it. How does it look to you? Maybe you think that this is good to be more aggressive and stay in the best shape for longer initially, or maybe you can wait. Just harvest and let's wait." These are personal and medical decisions, so I hope that helps, but clearly you can see there's no definite answer. 

Robin Tuohy: 

Yeah, and it's something that we're learning as we go. It does tell us there's choices and options for patients, so having those good conversations with your doctors, whether it's delayed or early, can really play a big factor in your quality of life. 

Dr. Brian G.M. Durie: 

Absolutely. Absolutely. If it's going to be delayed, as I said, only 20% of the patients in that trial when I had to do the delayed part, so if you're serious about the stem cell and really do think you want to do it later, just make sure that you get the stem cells harvested and then talk to your doctor about, "Okay, if we're going to do that stem cell, when would we think about possibly doing it?" You know. 

Robin Tuohy: 

Yeah. I think here's an important question about Dex because gee, that old drug Dex, it's still in use, right. Dr. Durie? 

Dr. Brian G.M. Durie: 

Yes. 

Robin Tuohy: 

One of the slides was a Polish maintenance study and it was a three-drug maintenance, and she's wanting to know because she lives in the UK, and she's wondering. Is that a low-dose Dex? 

Dr. Brian G.M. Durie: 

Yes, it is the low-dose Dex. Yeah, but I think that they decided to use the (KRd) because that's a regimen, but there's a lot of pros and cons about the Dex in the maintenance setting. Obviously in that particular trial, was it the KR or was it the (KRd)? Right? We don't exactly know that, so I would mention that in the SWOG trial that I led, the maintenance was actually Rd, so the maintenance was not just Rev. It was Revlimid plus once-a-week Dex, and that particular study did have unusually good results. 

I think this is another case where it's clearly optional to really not take the Dex, and I would strongly, strongly recommend that you not take any high doses of Dex for a very extended period of time because we know that taking Dex for longer than one to two years, for example, can have a lot of different side effects, on blood sugar levels, on developing cataracts, on loss of muscle, all kinds of different side effects, so I definitely do have a concern about ongoing Dex. I think in the maintenance setting, it's definitely an option to not take the Dex. 

Robin Tuohy: 

There you go. The good and the bad of Dex. Right? 

Dr. Brian G.M. Durie: 

That's right. 

Robin Tuohy: 

Okay. As I'm looking through here, there's some questions about MRD, of course, and using that as an endpoint and then circulating tumor cells and then the near and longer-term applications of the data in clinical trial decisions. 

Dr. Brian G.M. Durie: 

Right, right, right. Yeah, the MRD, is it ready for prime time yet? I mean, this is really a tricky point. We've been talking about minimal residual disease for quite a number of years now, so this is a very valid question. Is it ready for prime time because we're saying, okay, if a treatment gives MRD, this could maybe drive the decision process. I mean, is it ready for prime time? So unfortunately the answer to that is probably no in that all aspects of the MRD testing are not fully standardized yet. Just to jump ahead, we're trying to get that standardization achieved within the next year or two as a maximum, as quickly as possible, but what is not standardized, just so that people understand is when should the test be done? If you're MRD positive after your initial therapy, is that the time to do it, or should you get MRD testing when you're on maintenance to see if the MRD is going from positive to negative?  

The first question is when should you get the test done? Then the second relates to a lot of the technical details about the MRD testing. Right now, we do the MRD testing from the bone marrow, so there are a lot of technical details about collecting the sample. To be reliable, you actually need to take that first sample. When you do the bone marrow testing, take that first sample and send it for the MRD testing. A lot of sites, they don't do that. You need to be very careful about the collection and then sending it to the lab, and then you can get it done by next-generation sequencing and next-generation flow.  

The good news there is that next-generation flow, that testing system has just been bought by the company called Becton, Dickinson that standardize a lot of the blood laboratory testing that we use around the world, actually, so they are really strongly committed now to standardize the next-generation flow testing from the bone marrow and probably also from the blood. They already got approval in Europe, what's called IVD, so they already got approval for their kit to use next-generation flow in Europe, so they will be submitting to get approval to do it in the US. So as you can see, there's a work in progress here, and it is pretty frustrating that we talk about it a lot, and the data that we show is mostly from clinical trials, and in the clinic, it's not quite there. 

Robin Tuohy: 

So maybe Dr. Durie, as we wrap up, there are some questions in here. Even though this webinar is not specifically on COVID-19 and vaccines and boosters, I do see some questions in here, so can you give a two-minute update on your thoughts? 

Dr. Brian G.M. Durie: 

Okay, so for COVID-19. Yeah, so for the COVID, I think that things have changed a little bit in the sense that obviously we strongly recommend that patients get vaccinated and double-boosted, as a baseline to try to get the maximum antibody levels that you can. Fortunately, we do have this treatment, which is called Evusheld which can actually give you the antibodies, so if you're concerned that your antibody levels are not good, that you were taking treatment and you probably didn't get such a good response to the vaccination, you can go ahead and get the Evusheld. I think that's a very good idea.  

Now, beyond that, what should patients be doing? Well, I am worried right now that we're seeing quite an uptake, an increase in the number of patients developing infections with this BA.5 variant, so it's a new variant, which is obviously the last thing we want to hear about, but it seems to be quite infectious and many people are getting it. The good news is if you've been vaccinated and boosted, and if you've had Evusheld, chances are that you will do quite well. However, some patients have still developed a positive result. 

Something in the news just yesterday and today is that if you develop a positive test, this medicine called Paxlovid, which is an antiviral combination treatment, that is now going to be available through your pharmacist, so this is something to be aware of that you could get Paxlovid, that early treatment through your pharmacist. You could even think about getting it ahead of time because it's something that needs to be taken right away if you happen to get a positive test, so if you're planning to travel, it might be good to have a dose of Paxlovid on hand even or at least a prescription. Something to think about. 

Okay, so I think that we've run out of time here. I am hopeful that the CAR T-cells will be more available soon, that these supply chain issues will be solved. It's so frustrating that more CAR-Ts are not available when I show you all these amazing results and then it's so difficult to get. I do understand that, pretty annoying. 

Yeah, so people do have concerns about some eye issues with the Blenrep, and certainly this does need to be monitored closely with dose and schedule adjustments, just to make sure that you stay clear of any eye issues with that, but the doses and scheduling can be adjusted to try to minimize any impact from that.  

Okay. We can't cover everything. We will try to follow up with questions that we think are the most critically important. So, thank you all for joining this webinar today, and thank you so much, Robin, for helping field these questions. 

Robin Tuohy: 

Sure, absolutely. Thank you so much, Dr. Durie, and everyone for joining this evening. It really was a lot of information to absorb, a lot of hope for the future, so I'm glad we've recorded the webinar. The replay will be available early next week, so everyone can access that and all the previous webinars at myeloma.org and click on IMF Videos.  

Once again, we'll thank our sponsors for this educational presentation, and they are Bristol Myers Squibb, GSK, Janssen Oncology, Karyopharm Therapeutics, and Sanofi. Last but not least, please don't forget to provide us with your feedback and take the short survey at the end of this webinar. Dr. Durie, thank you so much for your continued guidance and support for all of us trying to live well with myeloma. I hope everyone has a wonderful rest of your day or evening. 

Dr. Brian G.M. Durie: 

Thank you so much, Robin, and I echo that. So have a good evening and moving into the weekend. Thank you all so much for participating today. 


With Support from:

Bristol-Myers Squibb, GSK, Janssen Oncology, Karyopharm, Sanofi

 


Source URL: https://www.myeloma.org/videos/best-2022-asco-eha-webinar