Dr. Brian G.M. Durie:
Welcome everyone to this review post-ASCO, post-EHA, and also the IMWG summit, which I'll comment on briefly at the end. If we can move forward here, I think the virtual ASCO was a very active meeting, even although it was not live, obviously. This year, over 4,000, close to 5,000 abstracts, which is down from normal, but still a substantial number of abstracts. For myeloma, 282 abstracts overall, of which 26 were oral, and you can see the other numbers for posters and publication only, so still a substantial number of abstracts with interesting and important data. Obviously, with 282 myeloma abstracts, I cannot be commenting on all of those, and so to anyone or any sponsor or anyone who is interested, please don't be offended if I haven't been able to go into detail about your particular abstract. It's just not physically possible.
What I'm going to do is to try to highlight what I think were really major topics, which will be broadly interesting for everyone. And so, as Robin mentioned, I will cover the immune therapies, CAR T, bispecifics, frontline therapy, triplets, and quad triplets, and then look at different aspects of new monitoring techniques, mass spectrometry and imaging, and several relapse therapies. Obviously there were many abstracts about different relapse therapies, but I'm going to focus particularly on these three new agents listed there, Ninlaro, Xpovio, and Sarclisa. Let's get right away to the immune therapies which have been the most interesting at our recent national and international meetings, and tremendous interest in the CAR T-cell therapies, and so these are obviously therapies using the patient's own T-cells, which have been genetically engineered against the target, and in this case, the BCMA, which is the B-cell maturation antigen, which is on the surface of myeloma cells, and is strongly expressed.
These are engineered patient T-cells against the BCMA, and so there are several of those products. This one is coming from the Janssen company and it's called cilta-cel, and the major trial, CARTITUDE, was presented this year at ASCO by Dr. Saad Usmani. Next slide. And so the overall summary I think was really pretty impressive, because the results were actually improved versus previous presentations. At this time, the median follow up, so the average follow up was a year and a half, 18 months, and at this point 98% of patients had an evidence of response, which means that the myeloma protein level dropped at least in half, and of those, stringent complete remission occurred in 80%. Really quite impressive, deep responses with this CAR T-cell approach. In addition, looking at that 18 month time point, 66% of the patients were still in remission, and so really very strong results, and these are the basis for submission to the FDA.
It's strongly anticipated that this will be reviewed by the FDA with an announcement of what is certainly hoped will be an approval, by the end of the year. There were some newer concerns, patients who are living longer, some did have some delayed, particularly neuro-toxicities, and there's some evaluation of what is behind that. Maybe linked to bridging therapies, and also the fact that many of these patients are coming into this treatment having very, very advanced disease with a lot of underlying toxicities from prior therapies, but there's tremendous interest right now in how to mitigate or prevent those moving forward.
Next slide, which is slide number nine. Now, the CAR T product which has already been approved by the FDA with a trade name of Abecma, ide-cel, there were four new presentations about this approved CAR T therapy. Really not providing a lot of strong additional data, but absolutely supporting the very strong efficacy of this product and indicating data in earlier disease settings, for example, CAR T-cell therapy in high risk, newly diagnosed myeloma, which is the bottom of these different abstracts that I list on slide number nine. Next slide, please. In addition, data were presented about the bispecific antibodies, and a bispecific antibody means that the antibody has two arms. One arm binds to the myeloma and the other arm binds to T-cells and brings them together, and so it really enhances the T-cell killing of the myeloma. This particular one, teclistamab, updated results were presented by Dr. Amrita Krishnan from the City of Hope. Next slide.
In these relapse refractory patients, 40 patients, again, really quite impressive results, 65% response rate with significant deep responses, but you can see 30% CR, stringent CR, so not quite as striking deep responses, but nonetheless really substantial response. Obviously this is a therapy, which is an ongoing therapy, and it's anticipated that there will be some ongoing and deepening responses over time. With this particular product, fortunately the toxicities have been acceptable and manageable, and so really quite promising. Next slide. Unfortunately, with this next one, Elratamab, very challenging name here, another bispecific. Unfortunately, by the time that this was presented, this study had actually had to close because of some ongoing toxicity, so unfortunately we're waiting to see what will be the future for this particular bispecific, which has had some significant neuro and other toxicities.
Next slide. It's helpful just to think about it a little bit and say, "Okay, what's next for CAR T?" Obviously, number one, we are anticipating the rollout of approved products. You'll see I have that in the plural there. We already have Abecma. Unfortunately, there have been some delays in the rollout, and so only a limited number of patients have been treated so far, and it looks like we're facing something like a smaller number of patients per month that will be able to get this Abecma CAR T therapy, but hopefully that will increase in the coming months.
We're hoping that if the CARTITUDE-1 study leads to the approval of that product, that will roll out by the end of the year into 2022, so it's hoped that in early 2022, there will be significant access to two CAR T products. Looking to the future, we will be looking to see earlier use of those products, and we will be expecting next generations to be coming along. As far as the bispecifics, where will they fit in? This is on slide number 14. The big difference here is that what people call a one and done, which is for the CAR T, that means they're just the single infusion of the CAR Ts, with the bispecifics there is an ongoing IV or subQ administration, and the big idea right now is how long will that be recommended? There's thoughts that perhaps six months will turn out to be a useful period of induction with this really powerful relapse therapy.
There are concerns about toxicities, particularly neuro-toxicities, but teclistamab, and I think a number of other products, will indeed move forward strongly. These are going to be complimentary immune therapies. I think that the big thing about bispecifics is that... The jargon for that will be is that they are off the shelf, meaning that they will be accessible when the patient goes into the clinic, and they will be able to get that right away rather than having to wait a number of weeks and hoping that the CAR T product will indeed be feasible. Next slide. I think we have a couple of minutes here. We can stop and see if there are any particular questions about CAR T-cells, bispecifics, or any of the immune therapies. I see someone's asking if they will be available in South America. I don't know about that.
I think that the big thing in Latin America will be to try to encourage ongoing trials until the products do end up getting approved. There are obviously access problems as well as expense problems, and then there's a similar question about the bispecifics. I think that the teclistamab is probably going to be the first that might lead to the approval of a bispecific, but a number of very promising bispecifics, and we have to wait and see which one will end up... But I would expect in 2022, we'll be reading more about that. What makes a newly diagnosed patient high risk? This is primarily related to those high risk chromosome test results, particularly chromosome 17 minus. Now we look also closely at problems with chromosome number one, and so it's based on what we call the FISH chromosome test results, and so this requires information from the bone marrow, which is done at the time of diagnosis.
It's a bispecific T-cell therapy. Now that actually is interesting in that the CARTITUDE CAR T actually has a double head on it, and so actually it is kind of a double CAR T, and that could be why we're seeing perhaps a little bit better results with that particular product versus the ide-cel, which is a singlehead product. At what point do the CAR T-cells get introduced? This is a very, very key point. If a patient is having a relapse and could be eligible to get the CAR T, what happens is that you have to harvest the T-cells, and then the patient gets what is called a bridging therapy. That bridging therapy to control the myeloma for a few weeks while the CAR T-cells are being engineered and grown up and sent back, that is a key thing, so you're talking about a significant process there.
Now, the approval for that has been going through in a pretty regular basis, so it does seem that a broad range of health insurance will cover that. I think that one of the issues is that the approval of the center, so that there are a number of these centers approved across a country, and so there could need to be a referral to the closest center which has an up and running approved CAR T program. Do I think that CAR T-cell therapy will eventually replace first induction? Probably not, but a lot of people are talking about how maybe CAR T-cell therapy, if it's well tolerated, could maybe be a new auto-transplant, so instead of doing an autologous stem cell transplant, people are thinking maybe a cool thing to do would be to use those CAR T-cells earlier, and they might be even more effective, and this could be an alternative to using autologous stem cell transplant.
Does CAR T-cell work for amyloidosis? I think we maybe just have a little bit of data that some myeloma patients do have amyloid, and I think there have been indications that that has also cleared, but it's not approved specifically for amyloid yet. The data and high risk disease is just early so far. Okay, so let's move forward. Those are some important questions so far, so let's move into the next segment here, triplets versus quadruplets, and we did have some really important data. I'm just going to touch on what I think are two very important trials. The first one on a triplet, and the second one on a quadruplet, a four drug regimen. The first one, three drugs, a triplet, daratumumab, Lenalidomide, and Dex. That's a Revlimid and Dex. It's a study, the Maia Trial, a phase three Maia study, and this has been led by Dr. Terry Facon from France.
A very, very successful trial, and so this is in patients who are not eligible for transplants, so this is for older patients, not transplant eligible. The results have really been quite impressive. Next slide. And so in slide number 18, I show you what has been the length of their mission, the progression-free survival, and you can see at 5 years, 60 months, 52.5%, so over half of the patients are still in remission at 5 years. This is really fantastic first remission for these older patients who are not transplant eligible, and so using daratumumab, Revlimid and Dex has really become, as it says here, a new PFS benchmark in this type of newly diagnosed myeloma who are not transplant eligible. Next slide, we'll see the overall survival, which is also fantastic at 5 years, 66.3%, so really outstanding results with this triplet therapy.
Next slide. Now, if we look at patients who are eligible for autologous stem cell transplant, in this setting, it seems that the quadruplet may have a strong advantage. In this particular study, the CASSIOPEIA study has been presented several times actually, but this time with a longer follow up, and in this case, the results continue to be really, really excellent, showing that the daratumumab plus Bortezomib, Thalidomide and Dex is obviously better than the triplet, so the quadruplet is better than the triplet. One interesting thing, next slide, is that... If we can go to the next slide, yeah. I think that the patients moved on to daratumumab maintenance, and it seems like the patients really did incredibly well if they had daratumumab initially, and then in the consolidation, and it wasn't clear how much added benefit there was with ongoing maintenance.
However, I think this is early and there were a number of different groups in these follow up groups, and so I think that my take from the myeloma experts who are listening to these data is that it's still not clear enough to say about the details of the daratumumab maintenance. I think people are still thinking that daratumumab maintenance is probably important, but now it's something that we need to look at perhaps a little bit more closely. Next slide. Yeah, so I don't know if there are particular questions about using three drugs versus four drugs. I went through that fairly quickly. Obviously, expert results with both of them, and obviously even for a transplant patient, you could potentially use three drugs and then follow up with transplant. I can see still some questions about CAR T. I think before CAR T, could ever replace stem cell transplant, we would need to have a lot of data, randomized trials, so that's going to be some time in coming, although there will be trials for which patients new patients might become eligible.
A question is how about daratumumab, Pomalidomide and Dex for someone refractory to Revlimid? And this is actually a very active and unapproved regimen, so if you've already taken Revlimid, daratumumab, Pomalidomide, Dex is actually a very excellent backup option with very good ongoing results. If a patient is refractory to Dara, is there any sense in trying Sarclisa? Well, I think the data on that is that probably is not a good idea to switch to it right away. However, for both of these agents, so Sarclisa is Isatuximab, and so this is another anti-CD38 monoclonal antibody similar to Dare. However, if you wait, there's like a washout period, then Sarclisa, which is the Isatuximab, the alternate, can work if you have a rest period in between. Obviously, Sarclisa is IV, and now we do have daratumumab available in subQ, which does have an additional attraction, particularly for patients.
Is there an advantage to continuing with four drugs where the transplant is not possible? I think that obviously those are personal things with your doctor, but that's exactly right, and so as far as transplant, one of the big things about transplant these days is if the four drug regimen has given a deep response with no residual disease and what we call MRD undetected or negative, then maybe you don't need to rush to do an autologous stem cell transplant. I do think that we'll see that the use of quadruplets will lead to a reduction in how frequently we do a planned first transplant early.
Okay. I don't see any others. Now, one other important question which I didn't touch on is that if you're high risk, how about using Kyprolis rather than Bortezomib? And so, yeah, a really excellent regimen for patients with high risk disease is to use Kyprolis, Revlimid and Dex, plus daratumumab, and so we do have excellent results with that. In the GRIFFIN trial, we have daratumumab, Velcade, Revlimid and Dex, and so then in the 4-T trial, we have Kyprolis, Revlimid and Dex, so that Kyprolis is also to be important as a triplet and as a quadruplet, especially if there's a high risk situation. Okay, let's go ahead into the next segment. We will have time at the end for some wrap up questions across the board. It was interesting to see this year, a bit more emphasis on new methods of monitoring, and it's particularly interesting to look at the use of two things here.
Where are we? Next slide. Yeah, so using mass spectrometry. Now, there is a very sensitive method... There's really two methods of mass spectrometry. One which is a little bit more sensitive than the other, so with the MASS-FIX, then this is something that's approaching a sensitivity similar to MRD. Dr. Dispenzieri from the Mayo Clinic looked at the results where mass spec, which is a blood test, was used to look at the level of the myeloma protein in the blood in a much more sensitive way. What she found out is that if you are negative with MASS-FIX or mass spectrometry in the blood, this really is quite predictive of a good response. In the STAMINA trial, which has been previously reported, it gives a very good follow up. She was able to say that actually, this negative result with MASS-FIX, or also the opposite, if it's positive, MASS-FIX negative was good and was what we call an independent predictor, so really a very strong indication that it's a useful thing to be doing.
It's an independent predictor of both length of the remission, which is PFS, and also OS, which is overall survival. They compared it, she compared it to MRD testing, and it was really quite strong in its correlation, and basically this simple blood test really is very much complementary in this assessment of deep responses. Next slide. We had another study from the Spanish, the GEM Spanish trial, where they basically found exactly the same thing with this peripheral blood mass spectrometry in this trial with newly diagnosed patients. Again, Dr. Noemi Puig, she found that... Yeah, you can go forward to the next slide. She found that mass spectrometry, very much complementary. Was helpful actually to have both results, the next generation flow, NGF. What that means is the bone marrow was tested using a flow technique, very sensitive, excellent information there, but also the mass spectrometry, and using both of those was really an excellent way to predict if a patient was going to do very well or not.
If it was negative, that was good. If it was positive, that was not so good. There were some patients who were negative with the NGF and positive with the mass spec, and this is being further studied now. Next slide. Yeah, so the other type of monitoring that we continue to look at closely is whole body MRI, so MRI FDG PET/CT, FDG PET. PET is a technique where you inject sugar, and so when you inject sugar, radioactive sugar, it tells you if there's any active myeloma. It's what we call a metabolic scan. MRI is more of a morphology, it shows the distortion of the born marrow architecture, and so if it's disturbed because there's a myeloma lesion, you can see that disturbance in the morphology. You have two different types of ways of looking at the myeloma tumor burden. And so what were key questions?
Well, if you want to look for myeloma lesions, the standard of care is to use whole body, low dose CT. If you're concerned, if the question is, do you have any active myeloma? If let's say the myeloma protein has gone up, or if there's a positive mass spec, a good thing to do would be a PET/CT to see if there's any active disease. What the imaging study showed was that if you do MRI, you might in fact find more lesions, but these may or may not be active, so the difference is the MRI picks up lesions, some of which are maybe responding to the therapy and disappearing slowly, and some of which may or may not be active, so it depends what your question is. If you're looking for active disease, you probably still need to do a PET/CT scan.
Okay, so I don't know if people have questions about this mass spec. Yes, is mass spec superior to free light chain test? Yeah, so mass spec is going to be very, very much more sensitive than the free light chain test, and so as soon as this becomes commercially available, which will be within the next year, mass spec will probably actually replace free light testing, so that's a very, very good question. The testing will probably be simplified where we'll just be able to use a mass spec. The other thing about mass spec is that it detects the myeloma protein specifically, and sometimes there's a confusion because these monoclonal antibodies like the daratumumab is a monoclonal antibody against CD38. It shows up as a spike in the blood, which can be confusing, and so the mass spec will tell you if the spike is the myeloma or possibly the leftover daratumumab from the last dose.
How common is MRD testing in patients who are not in trial? I think that still, since the MRD testing is not fully standardized in the clinic and still we are not 100% clear what we will recommend if the test is negative or positive, it's still not widely used as a standard test. We're trying to get FDA approval to use it as a surrogate marker for length of remission or PFS, but that probably will not happen until sometime next year. Will MASS-FIX eventually replace bone marrow testing? A good question. I think that if you have a positive mass spec, then it might be that you could skip the bone marrow test because [inaudible] you can still see there's a little bit of myeloma left, and so maybe you don't need to do that bone marrow test. I think it will reduce the need for bone marrows. Well, we still need to do bone marrows, but not as frequently. Yes. Okay.
Yeah. For patients on maintenance responding well, how often would you do the imaging? Well, I think that we like to do in patients, particularly who've had multiple lesions, we like to do follow up imaging once a year, and then only additionally if there's a concern. If the myeloma protein level is going up one month, two months, three months, then is a time to do a follow up PET/CT or MRI. Obviously it depends what's been done before. If you've had an MRI before, then you can repeat it and then you can compare. It's very important to be able to compare the new image with the previous one, so pay attention to what you've had done before.
Those are some of the main questions. Right now to get a mass spec test done, you can send the sample to the Mayo Clinic and it can be done as a routine matter, and so you can actually go to the Mayo Clinic testing website, and then you just mark the correct box and then you can send it into the Mayo Clinic. And they will send you a result with a report and a little bit of a discussion, so it can be done by sending it to the... Send it to the Mayo Clinic. The MALDI-TOF is just the type of the machine that is used for the mass spec testing, so that's just a particular type of method that is used. Yeah.
Okay. Some good questions there. Let's move forward to our next segment where we have a number of relapse therapies. Obviously at ASCO and EHA, there were a lot of abstracts about different relapse therapies, and so I'm only going to touch on a few of those, and so I apologize for some where I don't give full details, but I'm trying to focus on trials where there were some important information that might be pertinent for patients to be aware of. If we move forward, first of all with Isatuximab, what's called Sarclisa, trade name, Dr. Paul Richardson, he provided an update on the ICARIA study phase three in combination with Pom and low dose Dex, and so obviously this has been a very, very strong combination with added PFS benefit, and so well tolerated, excellent three drug combination.
You'll notice that with many of these, the Pomalidomide and the low dose Dex is what we call the partner, so many of these drugs are tested in combination with Pom and Dex, and we look to see whether the three drugs are better than the two drugs. In this case, strong benefit with three drugs. Next slide. Similar data for Ixazomib, which is basically a proteasome inhibitor, so it's a drug like Bortezomib and Carfilzomib, which are intravenous proteasome inhibitors. This one is by mouth, Ninlaro. Ninlaro, which is oral spelled backwards, if you look at the word, it's oral spelled backwards, which is a little bit of a trick there. Again, Paul Richardson presented the results of the MM1, which is the TOURMALINE study. Again, the three drug versus the two drug, and very, very striking PFS benefit, remission duration benefit.
There has been a strong motivation to see if this leads into overall survival benefit, and although there's a definite trend towards that, this has not reached a high level of statistical significance for this particular trial, but it really highlights the problem that we have because you see right now, there are so many new drugs available. If a patient relapses and then moves on to a new therapy, it actually becomes very difficult to assess the overall survival, because if they have an excellent therapy later, like daratumumab or something like that, then the overall survival could catch up, depending on which is the next therapy that's administered. And so, although there was just a trend towards overall survival benefit, I think the key thing is during the time that this three drug regimen is being used, there really is excellent length of remission, so I think that people are paying more attention to that.
Next slide, then a very interesting study TOURMALINE MM3 and 4, presented by Bruno Paiva from University of Pamplona in Spain. He was looking to see what is the impact of taking the Ixazomib, the by mouth proteasome inhibitor trade named Ninlaro, what is the impact of taking that in a maintenance setting? Next slide. Very interesting... Oh. Yeah. Very interesting results. There is a benefit in terms of the length of the remission if you take the Ninlaro, the Ixazomib, versus a placebo in patients who had residual disease. When they started on the maintenance, they had residual disease, which we call MRD positive, so minimal residual disease positive. Then when they took the Ixazomib, they converted to negative, and so those were the patients. In the chart there, you can see the two red lines are above the blue lines, and so the kind of middle red one is the ones who converted from MRD positive to MRD negative. Very encouraging for the value of Ixazomib maintenance in this setting. Quite interesting results there. Next slide.
Then quite a number of trials using Selinexor, which obviously was approved some time back now, trade name Xpovio. Next slide. Again you'll see here, this was presented by Dr. Darrel White from Dalhousie University, Halifax, Canada. Selinexor, Pomalidomide and Dex, you can see this is what everyone is doing. How does it perform in the triplet? Obviously there were excellent results with this three drug combination, and well tolerated with less nausea, and really with the three drug combinations they've been really tolerated remarkably well. Next study, there were a number of these studies. Yeah, so the once weekly Selinexor, which is very well tolerated, combined with Carfilzomib, so the IV proteasome inhibitor which is active in patients with high risk disease, heavily pretreated. Again, these were really excellent results, and so interesting to note that patients with high risk disease, so that Selinexor, because of its mechanism of action, has a tendency to be effective in patients who have high risk disease.
And so this combination with Carfilzomib, which is also probably more active in this setting, was giving good results in heavily pretreated and high risk disease patients, so very encouraging. Next slide. And then Professor Thierry Facon had a follow up basically from the BOSTON study where he looked at the patients who were in the older patient population. And next slide will see that what he found was that in patients over age 65, really excellent results, Selinexor combined with VELCADE and Dex. It was effective and well tolerated, and there was improvement in both the remission, the PFS, and the overall survival. I think that you can see that there are a number of potential options, so if a patient, for example, is not able to take Velcade anymore because of a neuropathy, you see very good results with Carfilzomib, and so you have a number of options to consider.
If you can't use a proteasome inhibitor for some reason, then you could try the Pomalidomide, so the partner with the Selinexor, despite a bit of flexibility, and all of these seem to be good options to consider. Next slide. Okay, so questions here on this segment. I noticed one thing I'll just comment on, which is quite important. We have it in the Myeloma Minute today. It's a question about Melflufen, which is the trade name Pepaxto, and the FDA did issue an alert about the OCEAN trial, which is an ongoing trial, using Melflufen where they were seeing increased toxicity, including deaths with this drug, and so the FDA has raised an alert about this. We're really waiting to see the full data and the follow up information, but for those who might be looking to use this type of an alkylating agent as kind of like a new formulation of a melphalan that was directly into the myeloma cell, some caution right now with this red flag warning coming from the FDA.
Just to be alert and say, stay tuned really for new information as to the significance of that, how important will that be? Will that just be a temporary hold, which does happen with a lot of trials, or will it be something that is potentially more serious? We really don't know yet. Do you recommend checking MRD status before doing autologous stem cell transplant? That is actually a good idea, because the outcome in that frontline setting is if you get MRD negative, particularly at that 10 to the minus 6, so zero out of a million, then that is the main thing that predicts an excellent outcome. If you are already MRD negative, then an argument can be made to perhaps harvest your stem cells and defer an autologous stem cell transplant till later.
Since there is kind of like a potential action item, I think it is very reasonable, and so then again, on the flip side, I mean, I think that if there's a question about residual disease or relapsing disease, this can be a situation also where checking MRD can be helpful to see, okay, is there recurring disease? Is the MRD positive now as a basis for decision making? There's some questions about this Melflufen which I mentioned, and we've entered into the chat box. It's called Pepaxto is the trade name, and it's melphalan flufenamide is what it is. Just to be aware that there's an ongoing question about that right now.
There's a question about a lady, a wife who is doing well with Carfilzomib and Isatuximab, but has had some cardiac issues. I think that that is a particular concern, and so I would be definitely cautious about that. I think that if there are ongoing cardiac issues, it's definitely a concern to keep giving the Carfilzomib, so really talk carefully to your doctor about the situation. It depends on the exact type of the cardiac side effect, but certainly a situation where it might be prudent to hold the Carfilzomib and maybe consider another combination with the Isatuximab because it's been used in combination with a variety of things. Yes, I'm looking at some of the other questions here. One broad question, why is a steroid Dex part of most therapies? Yeah. I mean, I think that for patients and for spouses, steroids Dexamethasone can be quite an issue. It has a lot of side effects, mood changes as well as things like effects on the eyes, it can cause cataract and also trigger sugar diabetes, and so why do we keep persisting with that?
Well, it really does enhance most every therapy that we use, and so it gives that little bit of added benefit. However, it's really important to balance against the immediate and potential future side effects, and so really low dose, which means once a week. In that schedule, the maximum dose is 40 milligrams, and I think that what I strongly recommend is to try to stick with once a week, if you can, but you can cut back the dose to 20 milligrams, to 10 milligrams. Well, it's a 4 milligram tablet, so you cut it to 12 milligrams or 8 milligrams or even lower. Just taking a much, much lower dose can give that added treatment benefit and really dramatically reduce the side effects, so this is something... Talk to your doctor about it, either reducing the dose, and if you're doing well, maybe try to get off of the Dex over time. But certainly initially for the first two or three months, it is worth having it in there to get that added response benefit.
Yeah, what represents heavily pretreated? Yeah, so that's a patient who's gone through four, five, six different combinations before, and so a lot of different regimens, exposure, so that... We use these words, one of which is exposure, which means that you've taken a lot of regimens and then there's refractory or resistance, which means that really they were used strongly and ultimately they were not working. Many times patients have been exposed to a lot of therapies, but you're not clearly resistant to all of them, and so sometimes we can use these drugs in different combinations and still have a good result.
Okay. Let me try to move forward just into a final segment here, and then we'll have time for some wrap up questions at the end. I just wanted to highlight some of the things that came up at our IMWG Summit, which is normally held along with the EHA, the European Hematology Association meeting. And we've touched on several of the things that we discussed in our working group sessions, but one I didn't go over is for patients with smoldering myeloma, I think that we now have more secure ways to diagnose who will progress using this 2/20/20 system, IgG of two, free light ratio of 20, percentage plasma cells in the bone marrow of 20. Patients who exceed that are likely to progress within 18 months to 2 years. We also have developed a scoring system where you add up the score of points for each one of those, and if the total score gets to be 12 or higher, then that's called ultra high risk.
This type of patient really is someone who needs to look carefully about the pros and cons of active treatment. Even although the disease may appear to be still smoldering, it's really turning active, and the question would be which type of therapy, something gentle like a Revlimid or even a Revlimid combination? Or we are looking at what we call our CURE trials, where we're giving a more aggressive approach in an effort to really have a decisive benefit in these patients. One thing which is going to be very important moving forward, coming out of our immune therapy committee working group led by Dr. Tom Martin from UCSF and Dr. Yilan from the Mayo clinic, is to have a registry for patients who are taking immune therapies. As these immune therapies roll out, like the CAR T-cells, the Abecma, and then the cilta-cel when it presumably will get approved.
And also we already have the Belantamab, which I haven't talked about so far, which is the antibody drug combination which is already approved. Belan maf, very, very active anti-PCMA therapy, we need to understand which patients will benefit the most from those, and particularly if patients are sequencing from one to the other, what might be the ideal sequence? If you've had one, well, maybe like a bispecific work, if you've had a monoclonal antibody, or... This registry will really educate us about what's happening in what we call the real world. When these therapies are rolling out into the community, how are patients really responding? What's the best sequencing, what's the tolerance, what's the efficacy? And we are very excited about this, and we're also setting up a biobank where we'll be able to look at what we call translational endpoints, look at what was the information in the bone marrow, and this is going to be quite exciting. Next slide.
Additional points, I haven't talked about a whole range of different monoclonal antibodies that are coming along, and a number of new agents I'd like to particularly mention, obviously the CelMods. Moving forward from the IMiDs, we obviously have Thalidomide, Revlimid, and Pomalidomide. Now we have these CelMods, which have a slightly different targeting, although they are still immune modulating agents, so to speak. We have two CelMods currently in trials, both look very encouraging and work after patients have received, for example, Pomalidomide, these CelMods, these newer types of immune modulating agents are working well, so there's quite a lot of attention about how are those going to play out over time. But before we close, I just want to touch a little bit on COVID-19 vaccination.
We had an excellent presentation at our summit from Dr. Evangelos Terpos from the University of Athens in Greece, and he talked about a couple of things. One, what are the neutralizing antibody levels in patients after the two dose vaccine like the Pfizer or the Moderna? I think that unfortunately the bottom line is that many patients did not have these higher levels that we would like to see, particularly patients who were on active therapy, particularly patients who were taking either daratumumab or these anti-BCMA type of therapies. And so this really, really raised the question of, "Well, how about a booster shot? How about a third booster shot?" And I saw there was a question in the chat box over to my right, and I think that I'm optimistic that one way or another, we will see an approval for patients like myeloma patients, so-called immune compromised therapy patients on active therapy where a booster therapy, a booster shot, which would be basically a third shot of either a Pfizer or a Moderna would hopefully boost the antibody level up into a safer zone.
Particularly with this Delta variant floating around in the community, trying to get those antibody levels a little higher will be good. Dr. Terpos in Greece is conducting a study to look at that. He's also going to be looking at in patients who are in a high risk category and there's a concern, maybe giving them a monoclonal antibody, an anti-COVID monoclonal antibody therapy. This is something that's a type of that's available from the Regeneron company. This was actually very much in the news, this is what President Donald Trump received when he went into the hospital. A number of people have actually shown significant benefit from this, and this is something to consider for patients with myeloma very, very promptly, if there is an infection which might occur. And so a lot of helpful discussion practical discussion about how to manage myeloma patients in this current COVID environment.
There are many additional questions obviously. My overall recommendation is that myeloma patients do need to stay safe. Even if you're vaccinated, I recommend that you continue to wear a mask when you're out in public, especially indoors, but really whenever you're in any kind of a risk situation, please continue just to wear your mask and practice social distancing and avoid large events indoors particularly, but really keep yourself safe as much as possible. Next slide. Yes, I think that we can have time just for a moment or two for just some closing questions. How can I get a booster shot legally? That's a little tricky in that it's not strictly legal right now. I'm hoping that the CDC will approve a booster shot.
The simplest thing, which I think could really happen very fast, is for there to be full approval of, let's say the Pfizer vaccine. Right now, it's available under what's called emergency use authorization, which under that, legally you can't get a booster, but if there was a full approval, the doctor would have the discretion to go ahead and give you a booster. I'm thinking that within the next few weeks, if those vaccines, Pfizer and Moderna could get full approval, then this would give flexibility to the doctor to legally give you a booster. Prior to that, it's possible that the CDC, they might authorize a booster sooner. There's been a lot of political pressure to try to make that happen.
Let's see what else. Yes, a lot of good questions about COVID and other things. Yeah, there's a question, it's probably a good time to perhaps defer a stem cell transplant. I would suggest continuing to stay safe for the next couple of months or so until we see what the ultimate level of the Delta variant turns out to be in your particular community, but really, with all these cases coming into the hospital, it's probably a good time to stay out of the hospital, for a couple of months anyway. And talk to your doctor about that. Yeah, are we close to having a blood test for MRD? Yeah, so the mass spec is pretty good. Also, we are looking at measuring plasma cells in the blood using a very, very sensitive method down to 10 to minus 8 even, and so the team in Pamplona is looking at that with Dr. Bruno Paiva, and if that works out, that would be truly amazing, and it would make such a huge difference where we would not need to be doing the bone marrows. We could monitor in a sensitive way, accurately in the blood.
Yeah, for myeloma patients who have not responded to the vaccine, could they get the Regeneron product? Yeah, so that's what I was talking about, and so if there's any concern, that would be a situation to consider doing that in a preventative way. Something to talk to your doctor about, to be aware of, because that is commercially available. Yeah, and there are a lot of questions about, should you take daratumumab right before you get your COVID vaccine? That's probably not the best idea. How long would you need to be off of it? We don't really know, and so there's a lot of questions there. In general, it means that patients need to try to stay safe, and as I say, I am optimistic that getting authorization for the booster will be an important step forward.
I think that we're going to have to stop there right now. We'll try to cover additional questions through our information line or info line or hotline and get back with results. A lot of really, really excellent questions, but clearly what we want to do in closing is to, again, thank our sponsors, Amgen Oncology, Bristol Myers Squibb, Janssen, Karyopharm, Oncopeptides, and Takeda.
We are very pleased that you were able to participate this evening, and we have a lot of information on our website. Please contact us and we'll try to follow up if you have particularly urgent questions in particular, so thank you and have a good evening.