Jenny: Welcome to today's episode of the HealthTree Podcast for Multiple Myeloma, a show that connects patients with myeloma researchers. I'm your host, Jenny Ahlstrom. Before we get started today on the show, I'd like to make a short announcement that we're beginning our ten-year anniversary celebration. We started HealthTree for Multiple Myeloma, and you might know it formerly as Myeloma Crowd in late 2012. It really never could have imagined that it would become what it is today. We have so many programs to support you, like our patient navigator team, our HealthTree Coach program, HealthTree University, our news website, this podcast, our live Round Table meetings, our HealthTree Moves app, HealthTree Cure Hub, and our incredible webinar events and chapters, which will reach, in total, over a million users cumulatively to those programs this year alone.

We now have a staff of over 60 people that that are incredibly happy to support you. If you have benefited from these programs, we invite your support or the sharing of our new fundraising campaign with your family and friends. Our goal is to raise $500,000 before year end. You can donate by clicking on the top right donate button on the website, which is at healththree.org/myeloma, and know that 100% of your donation will be used to further myeloma research that we are doing jointly with myeloma researchers. Thank you in advance, and for your consideration.

Now, onto our show. Having a new multiple myeloma treatment is very exciting. Recently, teclistamab was approved by the FDA for myeloma. This is the first bispecific antibody. We are so pleased to have Dr. Alfred Garfall with us today to share more about this new therapy. Dr. Garfall, welcome to the program.

Dr. Garfall: Thank you very much. It's so nice to be here.

Jenny: Well, we so appreciate you taking your time out. I know you're getting probably hounded by people asking you about this approval since you were helping lead this clinical trial, but I just want to give a short introduction for you before we get started. Dr. Garfall is Director of the Autologous Bone Marrow Transplant Department at the University of Pennsylvania, and Assistant Professor of Medicine at UPenn. He's a member of the Clinical Trial Scientific Review and Monitoring Committee, member of the University of Pennsylvania Institutional Review Board, and he performs teaching and mentorship of UPenn fellows in hematology and oncology.

He has performed publication review for many major blood cancer publications including Nature Medicine, Lancet Hematology, Blood Advances Leukemia, Clinical Cancer Research, and the ASCO Self-Evaluation Program myeloma chapter. Dr. Garfall graduated with honors from Princeton University, and has won awards including the Career Development Award from the Conquer Cancer Society of ASCO, and the Scholar and Clinical Research Award from the Leukemia and Lymphoma Society, in addition to many others.

With UPenn, really, in my opinion, leading the way on CAR T therapy and in immunotherapies globally, Dr. Garfall has been deeply involved in CAR T and other immunotherapies as early as 2014. He was the primary investigator on the teclistamab trial, so we're very fortunate to have him with us today. Dr. Garfall, maybe we want to just start by giving a broad overview. Since this is new in a drug class, can you explain what a bispecific antibody is in myeloma and how it works?

Dr. Garfall: Sure, of course. Bispecific antibodies are a class of cancer therapies where the antibody has two targets. We're used to thinking of monoclonal antibodies for cancer like daratumumab, where the antibody recognizes one target, and that target is a molecule on the surface of multiple myeloma cells. In the case of daratumumab, that molecule CD38. When you give that antibody as a drug, that antibody will bind to CD38 on the myeloma cells, and then that antibody will flag those myeloma cells for certain parts of the immune system that can come in and attack the myeloma cells, just the way an antibody against the virus or a bacteria would work. That's how conventional antibodies work.

The parts of the immune system that conventional antibodies activate are parts of what we call the innate immune system, like natural killer cells and macrophages. Those cells are able to kill multiple myeloma cells in response to antibodies like daratumumab. What we've learned over in recent years, however, is that another part of the immune system called the adaptive immune system and specifically T-cells in the immune system, they're able to kill cancer cells a little bit more potently than the innate immune system. Bispecific antibodies are a way to get in the form of an antibody to get the T-cells in the immune system to recognize the cancer rather than just the innate immune system like regular antibodies do.

The way bispecific antibodies are formatted is that they have two targets. One target is on the multiple myeloma cell, just like a conventional antibody. But the other target is a target on a T-cell. You can think of these antibodies as having two arms. One arm grabs the myeloma cell, and one arm grabs the T-cell, the cell on your immune system called the T-cell, and forces the T-cell to come over to the multiple myeloma cell, to get activated and kill them multiple myeloma cells. The bispecific antibody serves as a bridge between the T-cells and the multiple myeloma cells to get the T-cells to kill the multiple myeloma cells. That engagement of the immune system seems to be a bit more potent than the type of engagement you can get with a regular monoclonal antibody like daratumumab.

What we've seen in clinical trials now, with several different bispecific antibodies in multiple myeloma is that in patients with what we say relapse disease, people with more advanced myeloma, the kind of patients that enroll on Phase I clinical trials, you see most of the patients on these trials responding to these bispecific antibodies or we didn't see such high response rates when traditional monoclonal antibodies were tested in multiple myeloma. In fact, what we see with bispecific antibodies is the same kind of T-cell activation against the myeloma that previously, you could only get with CAR T-cells.

CAR T-cells may turn out in the end to be a little bit more potent than bispecific antibodies, but bispecific antibodies are probably pretty close. What's amazing is that you can get that activation of T-cells against the myeloma in the form of a drug that you can just give it a subcutaneous injection, rather than the more complex procedure that you have to go through to get CAR T-cell therapy, which requires collecting T-cells from you waiting, sending those T-cells off to a company to go through a manufacturing process, and then waiting for them during that time, and then getting the T-cells back and introduced to you. It's still a very effective therapy, but a little bit more of a complicated process. The idea that we can get that same kind of T-cell activation against the cancer in the form of a drug that we can just give as a subcutaneous injection is really a big step forward.

Jenny: Well, it's a huge opportunity for a lot of patients who either can't qualify for CAR T or it's not available for CAR T, so this is a great additional option for patients. I think it's pretty exciting that it's out and now approved. Can you talk a little bit about the BCMA as a target, just generally speaking, because we know it's a target for an antibody drug conjugate, and we know what's a target for CAR T, and now it's a target for bispecific antibody. Can you explain just a little bit about the target, and why this target is important, or why it was chosen?

Dr. Garfall: Sure. As I mentioned at the outset, all antibodies that target multiple myeloma have to recognize the multiple myeloma by some kind of protein that's on the surface of the multiple myeloma cell. That's how the antibody can recognize myeloma and not recognize other cells in the body. I mentioned that daratumumab, an antibody that's been around for a little while, multiple myeloma recognizes CD38. There's a whole new way that the immunotherapies that are coming out, including the CAR T-cells that are already FDA approved, teclistamab, and then a whole -- belantamab, which is an antibody drug conjugate, and then many more coming down the pike, other bispecific antibodies that are similar to teclistamab. They work by recognizing the myeloma by BCMA.

BCMA, which is an acronym for B cell maturation antigen, this is a protein that's on the surface of multiple myeloma cells. What's nice about it, as an immunotherapy target, is that it seems to be very nicely restricted to myeloma cells and normal plasma cells. There may be some bit of expression of other cells of the body, but there's not a lot of it. That makes it a safe immunotherapy target. Because we know if we develop a therapy that targets BCMA, it's mainly going to target multiple myeloma cells and their normal counterparts. It also is going to target normal plasma cells.

That is where some of the risk of these BCMA therapy, directed therapies, comes into play, is that we also expect them to kill normal plasma cells in the immune system. Normal plasma cells in the immune system are the cells that are responsible for making antibodies that help fight infections. Patients that get immunotherapies to target BCMA often have low antibody levels. As a result, increased risk of infection. That certainly was seen with teclistamab. But BCMA is a marker that's on the surface of multiple myeloma cells. It has functions in how plasma cells work basically in the immune system. It connects with certain other components of the bone marrow to help plasma cells stay healthy in the bone marrow. That's its role in normal biology. It also probably helps multiple myeloma cells grow a little bit more. That's another reason why it's a good idea to target BCMA.

There's lots of different therapies that are being developed against BCMA. We already know about CAR T-cells that are FDA approved, the antibody drug conjugate belantamab, now we have teclistamab, and there are more CAR T-cells and bispecific antibodies coming down the pike that target BCMA.

Jenny: Right. It seems to be these bispecific fields targeting BCMA. Well, other targets too, right? But it seems to become a pretty crowded field. When you look at like proteasome inhibitors, you have like Velcade or carfilzomib. Those work really quite differently, but they still are both proteasome inhibitors. Do you see that same thing in the bispecific antibodies, or are they more similar? I'm just curious about that.

Dr. Garfall: It's really early to tell, because I think there are at least half a dozen of these bispecific antibodies targeting BCMA that are in various stages of clinical trials. We know just little bits of information here and there about them. From what I can tell, their clinical activity seems similar. But they haven't been directly compared to one another. It'll be a long while before we get any real sense of whether one is more potent than the other. But I think they all are similar in terms of their -- if you look at the response rates from the clinical trials that have been reported, similar response rates, similar side effects and toxicity profiles.

Jenny: It'll be interesting to see how that all falls out, because it seems like it's like a race on the bispecific antibodies. Teclistamab was the first approval. Let's talk about the approval a little bit. How was it approved? For what type of patients?

Dr. Garfall: Sure. It was approved, and you were very generous about our contribution to the clinical trial. But I'll just emphasize that this was a big global clinical trial that led to the approval of teclistamab. We were significant contributors in terms of the number of our patients who enrolled on the trial, but there are also other major sites in the U.S. and around the world that contributed. Of course, this study was led by Janssen Pharmaceuticals, the company that makes the drug. Obviously, they had an enormous role in developing the medicine.

It was approved based on Phase I and II trials. The first phase of any new drug being developed is just to find the right dose and assess whether it's safe. There were a couple of years of treating patients with teclistamab, with initially very low doses until the trial finally got up to a dose that seemed to give reliable responses and have an acceptable safety profile. Then, the Phase II portion of the study entailed treating a larger number of patients with that dose that had been determined to be safe and effective, and seeing how those patients did.

Those patients were mainly patients who had had all the major drugs from multiple myeloma. If you think about the major medications, being immunomodulatory drugs, like lenalidomide pomalidomide, proteasome inhibitor like bortezomib and carfilzomib. When the FDA looked at the data from the clinical trials to decide where they would officially approve and what patients they would officially approve the medicine, they approved it in patients who have had four or more prior lines of multiple myeloma therapy, which is a rough way of saying for more different regimens or combinations of therapies in the past, and still had disease that was progressing after that. That was roughly the patient population that was in the clinical trial.

Jenny: When they got approval, it's the same, right? It's four or more prior lines of therapy?

Dr. Garfall: That's what the approval says. That is a similar language to the approvals for belantamab, which is the antibody drug conjugate that targets BCMA, and also the two CAR T-cells that are FDA approved, and I think selinexor also. Now, we have several medications or therapies that are approved for that cohort of patients.

Jenny: Okay, wonderful. Just so patients know about prior lines of therapy, you can say you got like Revlimid, Velcade, dex, like RVD, and then you go to a transplant, and you get maintenance therapy, and that's called consider one prior line of therapy. It's not that just one time use dara and one time you use a proteasome inhibitor. I think sometimes patients don't know that. You'll need to talk to your doctor about it if you've had four or more prior lines of therapy. If that's considered prior lines, so just that's something for patients to think about.

Dr. Garfall: I agree. It's getting a little more complicated too, because now, it's often the case that patients are treated with -- we've learned over time that combining therapies early on is sometimes very helpful. You see, it used to be that you would get Revlimid and dexamethasone first, but now we do Revlimid, Velcade, dexamethasone, and even now, we're sometimes adding daratumumab into the mix. You can have a patient who's only had one line of multiple myeloma therapy, but they've actually been exposed to three or four major drugs. We shouldn't think strictly about lines of therapy when we think about treatment options.

This aspect of treatment planning has to be discussed in a personalized way. Sometimes, we are successful. The FDA approval doesn't restrict physicians' ability to prescribe medications, but it sometimes is what insurance companies use for guidance about what's a justified use of the medication that they would reimburse. We're sometimes successful in requesting approval from an insurance company to give a medicine for a patient that is slightly outside what the FDA put in the label.

A good example of that multiple myeloma would be maybe somebody who's had only two or three lines of therapy. But in those two or three lines of therapy, the patient has received every major multiple myeloma medication. It's just that those medications have been combined into two or three lines of therapy. We have sometimes been successful in obtaining coverage from insurance companies. I think that's a medically justified thing to do for some of these more advanced therapies if patients really have moved through all the major multiple myeloma therapy, they've just done it in two or three lines of therapy rather than four.

Jenny: That's a really important point that you can go talk to your doctor about that, and not make an assumption. I think some of these approvals, it seems like they're all approved in later lines of therapy, and then the companies are still working hard to do clinical trials that are using them in earlier lines of therapy, but they always have to start later for safety and those types of reasons to compare it to -- is this better than what we already have in our arsenal before they move it up, right?

Dr. Garfall: That's right. It's important to note that a lot of these therapies have received what the FDA terms accelerated approval, meaning that the results looked quite good in studies where patients with advanced disease got the medication, and had a response, and seem to tolerate the medication well, and had a good safety profile. But those clinical trials that lead to these accelerated approvals, and teclistamab is in this category, those are not comparative trials. These were not trials where teclistamab was being compared against something else and proven to be better than the alternative.

Ultimately, what is required for full approval is a comparative study, were teclistamab is compared to something else, some other standard of care, and found to be better than something that has already been proven to be safe and effective. That's really important, because we've had some instances in cancer medicines and in multiple myeloma therapies where medications that were given this accelerated approval, upon further study, turned out to not be as effective as they were initially thought based on the accelerated approval. Those other studies that you mentioned that companies are undertaking, those are often testing the new medication in an earlier line of therapy, but they're also comparing the medication to another established therapy to prove that it's at least as safe or arguably safer, and at least as effective or perhaps more effective than some alternative.

That's ultimately the kind of evidence we need to be really sure that the medication that we're using is safe and effective. But these accelerated approvals are still very important because a lot of them are later confirmed. By allowing the accelerated approval, it allows patients who really need something now to get access to the medication based on the preliminary information from these early stage one and two studies before the full phase three studies are complete. That availability can be life saving for some patients.

Jenny: Absolutely. All great points. Let's talk about teclistamab's administration. How is this drug administered and how frequently?

Dr. Garfall: It's given as a subcutaneous injection, which is -- I just have to say really amazing, as I mentioned, the contrast between the complexity of -- to get that effectiveness and activation of T-cells against the multiple myeloma in the form of a simple subcutaneous injection is really amazing. It's given as a subcutaneous injection. With teclistamab and other therapies that activate T-cells against myeloma, you run the risk of some of these inflammatory side effects with the initial dosing.

If your listeners are familiar with CAR T-cells, of course, you worry about cytokine release syndrome, which is the syndrome of fevers that can potentially progress to more concerning features like low blood pressure, difficulty breathing. It's even occasionally fatal. But usually mild and manageable, but occasionally fatal. Those are reactions that tend to happen early on with therapies that activate T-cells. Something that happens early on after CAR T-cell infusion. With bispecific antibodies, you get the same risk of cytokine release syndrome. There's also a neurologic toxicity that also goes along with these intense activations of the immune system that we have to watch for. Again, usually doesn't happen. If it does happen, it's usually mild and manageable, but occasionally, it's severe and even potentially fatal.

In order to reduce the risk of over activating the immune system early on, most bispecific antibodies that are being tested for multiple myeloma, are given and will be called step-up doses or priming doses, where before you get to the full dose of the medication, you're given a couple of smaller doses. The way the FDA has instructed us to administer teclistamab is to give -- and I'm going to use these units of milligrams per kilogram, but it's to start with dose called .06, and then give a dose called .3, and then a dose of 1.5 milligrams per kilogram. We give those doses a couple of days apart.

 It's suggested that patients be in the hospital for that time, so you would come in the hospital, get that first small dose, and the subcutaneous injection, wait at least two days to see if there's any cytokine release syndrome or neurologic toxicity that develops. If that develops, we let it run its course and treat it, and then when that is settled down, you can give the next dose, wait 48 hours, see if any of the side effects develop, and then once they've passed, or at least 48 hours later, give the third dose, which is the full dose of 1.5 milligrams per kilogram.

In the best case scenario that plays out over six days in the hospital, where you get a dose on one day, you get a dose two days later, get a dose two days after that, and then be observed for two days after the last dose, and then you can be discharged. Then after that, you would return to the outpatient clinic and receive the subcutaneous injection weekly. The way the FDA approved it is weekly subcutaneous injections as long as it continues to work indefinitely.

Dr. Garfall: I suspect with time, we will space out these doses once patients respond. That's definitely taken place in the clinical trial where patients who are in good responses have been able to reduce the frequency of dosing to every two weeks or even every four weeks, and maintain good responses that way. But right, the way it's officially dosed in the prescribing information is once weekly indefinitely.

Jenny: Well, I like the step-up dosing idea. I mean, it does make things a little bit more complex about how it's given, and you're in the hospital a few days over time, but I think that's smart, because I've had a friend who did a different bispecific antibody through trial, had a very big response, but then didn't have any other CRS or neurological response after that. It seems like, it's not like you were saying before, it's not as high as a CAR T, for example. But it can happen. It's smart that they're doing the step-up dosing.

Dr. Garfall: Yes. Those side effects tend to be confined to those early doses. It's possible after you leave the hospital, you might get a little cytokine release syndrome within the first month or so, but for the most part after that, you don't have any of those severe or concerning side effects. It is a little bit of an investment in the first week just to get the medication started safely. But fortunately, once you get past those first few doses, the risk of that happening is very low and it's very safe to give the medication as an outpatient.

Jenny: Great. I have a question. Are you saying as you're dosing or doing the step-up dosing, does this cytokine release, or CRS, or the neurological toxicities, does that have anything to do with tumor burden that you're seeing patients come in like, oh, I have a very high tumor burden, and I have more of that, because that's what they're seeing a little bit in CAR T, right? Is it the same?

Dr. Garfall: Yes. I would say that most of the patients on a clinical trial, because they had relapsed refractory multiple myeloma, had a fair amount of tumor burden. There's obviously a range there, but these are all patients with really active multiple myeloma. I can't say off the top of my head if they've done an analysis about the risk or intensity of cytokine release syndrome, according to say, how many plasma cells are present in the bone marrow.

In the teclistamab study, about 70% of patients had cytokine release syndrome. It was almost all low grade, meaning that they didn't develop any of the more severe complications of cytokine release syndrome. But about half the people who develop CRS had significant enough abnormalities even if they didn't reach the official criteria for high grade, there were significant enough abnormalities that warranted us giving that antidote to cytokine release syndrome, that tocilizumab antibody that can calm down some of the inflammation. Basically, 70% of people get CRS, about half of them required the intervention of that antibody. But I don't know exactly how that breaks down in terms of tumor burden or risk factors for that.

I would say that just in my experience taking care of patients with the medication, even if there are some rough correlates that it's not, I would say, reliably predictable. We had some patients who had a high tumor burden and didn't develop a lot of CRS, other patients with low tumor burden who did. What's also interesting is that the dose association is really interesting. We have some patients who, after that first or second really small dose, have significant cytokine release syndrome.

If you really check their multiple myeloma markers really early, after that second dose before the third dose, you'll see that they've responded to those tiny doses. Other patients, they don't develop CRS until they get the full dose and they don't respond until they get the full dose. We've even had some patients who were delayed in their response even a month or so, while the drug built up in their body. At least so far, I haven't seen anybody come up with an explanation for this. But a real difference between patients in terms of what dose is able to activate the immune system and generate both the myeloma response and some of the side effects that go with it.

Jenny: That early versus late response will be interesting to see like prolonged responses doesn't have any impact at all on how long you respond. That's super interesting. Well, you talked about that patients will receive it until they progress. I know there's a lot of talk about looking at MRD situations like, okay, if I'm MRD negative for two years, do I stop? If I continue to be MRD positive, I probably want to stay on treatment. But do you have any thoughts around how long a patient might end up being on it? I guess it's too early to say maybe.

Dr. Garfall: It really is too early to say. I would say that patients who respond tend to have very good responses, and often complete responses. Those responses are very durable. I think that the estimated something like 70% of patients who responded at 12 months were still in a response, which is really impressive considering that these patients were patients who had been refractory to a lot of other prior myeloma therapies. Is it possible that you could stop the medication and that the response would persist for a long time? It's very possible for those patients who are in deep responses.

I don't think we know yet how to make those decisions. There are some other bispecific antibodies that are being -- teclistamab was tested as an indefinite therapy. You keep getting it as long as you're progressing -- sorry, as long as you're responding, unless you have side effects that weren't stopping. We've definitely had patients who have had infections and COVID-19, and they had to stop it for a while. Those patients tended to remain in remission while they were off it, but once they recovered from whatever side effect or infection, they resumed teclistamab.

I believe we're going to see at ASH this year, some data with cevostamab, which is another bispecific antibody, where the way that is given on the clinical trials is that you receive it for -- if you're responding, you receive it for a while. I think it's 18 months or so. But then, if you're in a response, you stop it, and then you wait, and if the disease starts to grow at some point in the future, you can resume the medication. I believe in the ASH report this year that we should get next month, they talk a little bit about how those patients did, who stopped it, and how long they stayed in remission after stopping it, if they were in a good response, and how they responded, if they've progressed, some of those things that we need to know, to know if we need to continue it forever, or can stop it. That's going to take some time to figure out.

Jenny: Well, definitely. This was approved as a single agent drug by itself, and not in combination. We know that most myeloma therapies are given in combination. That's not really -- is it possible to give it in combination with something else, or a doctor just wouldn't do that? They would just try it by itself, because that's how it's approved?

Dr. Garfall: For now, as it's approved, it's approved as a monotherapy, meaning that you're not giving it in combination with anything else. There are studies going on testing combinations to see if that helps. But you always have to -- I personally wouldn't do that right this minute with this medication outside of a clinical trial, because with any new combination comes some risk. If you're not sure that it works better as a combination, it can be a little bit risky to try it as a combination, you might get some side effects without any benefit.

Inevitably, with new drugs, as you said, they get tested in combinations. I think we'll pretty quickly learn which combinations make sense and which combinations are safe and effective versus which ones -- maybe there's not a lot of good interaction between the combined -- as the number of myeloma therapies increases, it becomes a little bit more sprawling, all the different potential combinations, and it's going to take some time to figure out what's good combinations.

Jenny: I've heard people say, like, oh, we don't really want to use dex with any immunotherapies, because that may be damaging. We just don't know at this point what it can and can't be combined with.

Dr. Garfall: Correct. Now, I will say that with the initial doses of teclistamab, there is some dexamethasone that's given to reduce the risk. Yeah, just with the first couple of doses, with those initial step-up doses, there's some dexamethasone pre medication given. That's how it was done in the clinical trials with the idea of reducing the risk of allergic reactions and reducing the risk of severe abrupt cytokine release syndrome. It's possible that those dexamethasone doses aren't necessary, but for now, they're included in the prescribing information, but it's really a small amount of dex in the big scheme of things, and the ongoing dosing, which patients who respond will likely be on it for months or even years. There's no ongoing weekly dexamethasone, like there is with so many other multiple myeloma therapies.

Jenny: Wonderful. It is basically its own maintenance therapy, because you're staying on it. When we talked about side effects, you outlined three major areas – cytokine release syndrome, which is like you mentioned was like the fever and the chills and that type of thing, then the neurotoxicity potentially, sometimes if patients hear the term ICANS, that's probably in that same group. I can't even remember what that stands for, but maybe you do.

Dr. Garfall: It stands for immune effector cell-associated neurotoxicity syndrome. It's basically a set of neurologic side effects that can happen with these immunotherapies that activate T-cells. It was first reported with CAR T-cells, but also with bispecific antibodies, and it can cause anything from very mild confusion, that very short lived, to more severe complications like swelling of the brain that can be potentially fatal. As I said, fortunately, with bispecific antibodies, the risk is a bit lower. With teclistamab, they found very little ICANS, and that tended to be low grade.

There are a couple of other neurologic toxicities that have been reported, including with teclistamab, with different BCMA directed therapies, both to CAR T-cells and the bispecific antibodies. This wasn't from the clinical trial data, but it came out in the training that the FDA sent out to physicians about to teclistamab that there was one case of something called Guillain-Barré Syndrome, which is an auto immune type neuropathy that causes weakness, and in this case, it was fatal. That was just one reported case, but something like that has been seen with some other BCMA directed immunotherapies either bispecific antibodies or CAR T-cells. It's believable that that reaction was related to the drug. We are really careful to watch for these different neurologic toxicities, ICANS and then some of these other weirder ones that have been seen just with BCMA directed therapy so far.

Jenny: You said that the CRS and the ICANS resolve earlier and that infections might be just later just because it's ongoing, and the immune system is involved in that. Is there anything else that patients should be aware of as they select the therapy?

Dr. Garfall: The infections may warrant a bit more discussion because we're used to thinking of infections as a risk factor of all multiple myeloma therapies, but I think the risk of infection with teclistamab is a bit higher than the risk with other multiple myeloma therapies like daratumumab and carfilzomib. There were a fair number of patients who got infections with teclistamab including serious infections. This trial took place amidst the COVID 19 pandemic. Sadly, several patients on the clinical trial died of COVID 19. Then, we also have seen some opportunistic infections, infections like pneumocystis pneumonia. Opportunistic infections are infections that tend to occur in especially immunocompromised patients. A type of pneumonia called pneumocystis pneumonia, there was one case of a brain infection called progressive multifocal leukoencephalopathy, which is a viral infection of the brain that is often fatal, and it was fatal in this case.

With prolonged exposure to teclistamab, there is a significant risk of infection. There are some things that that patients should do to reduce the risk of infection. With COVID-19, we really want all our patients to get vaccinated against COVID-19. With our patients getting teclistamab, we've been very diligent about giving them Evusheld because patients with teclistamab really cannot make their own antibodies because of the effects of the drug on normal plasma cells. Evusheld is the way to get a dose of COVID antibodies, in case the vaccine doesn't make antibody, doesn't induce your body to make its own antibodies. We've been giving patients Evusheld.

In patients who get COVID-19, we've been very proactive about prescribing Paxlovid, the antiviral medication that reduces the risk of progression to severe COVID-19. Then, really encouraging patients to be diligent about COVID-19 prevention. We've been giving patients a prophylactic antibiotic that reduces the risk of that particular pneumonia type, pneumocystis pneumonia. I've been giving patients Acyclovir or a similar medication to reduce the risk of shingles or herpes virus reactivation.

Most of our patients are also receiving intravenous immune globulin, which is an antibody replacement therapy, basically giving you -- we can give red cell transfusions when you're low on red cells, we can give antibody transfusions when you're low on antibodies. Because this medication reduces your body's ability to make antibodies in such a profound way, we've been pretty proactive about giving patients intravenous immune globulin to replete their antibody levels, especially if they're going to be on the medication for a long time. Those are some of the ways we've tried to prevent infection. But still, some of our patients have gotten infections and even severe infections.

The other side effect to be aware of is some low blood counts. Most of the patients developed some form of low blood counts, especially early on. Some patients have required transfusions, especially in the first couple of months, and in specifically low neutrophil count seemed to be a problem. It's a very manageable problem. It can be a little bit random, so patients can have a fine neutrophil account early on, and then suddenly, they're getting the medication for a while and they develop some low neutrophil counts, you might have to hold a dose here and there. Sometimes, patients have required filgrastim, or Zarxio, or Neupogen to boost the white blood cell count. Unfortunately, the neutrophil count responds very promptly to filgrastim, or Zarxio, or Neupogen, whichever name you want to use for it, when it's needed, but that's something that we've seen commonly and can occur early, can occur later on, but it's very manageable.

Jenny: I have a question too. It sounds very similar to a lot of the CAR T side effects, in some instances, I guess, very rarely. But they might take some bank stem cells that you have like for a transplant, that have been reserved for transplant, and use them? Do you ever do that what the bispecifics?

Dr. Garfall: I've not heard of that being required for bispecific antibodies.

Jenny: Not required, but just doing it if patients have really low counts.

Dr. Garfall: Got it. No, I've not heard of that being used for bispecific antibodies, that approach. In the case of CAR T-cells, we've had a couple of patients who have had that complication of CAR T-cell therapy. I would say that's a more severe problem than what we've seen with teclistamab. With teclistamab and other bispecific antibodies, it's been, I would say not quite as severe or long lived as we've seen. Very few CAR T-cell patients who have had that problem where just all their counts, their white blood cell count, red blood cell count, platelets, all very low for a long time, you do a bone marrow biopsy, and it looks like the bone marrow is really suppressed. That is a relatively uncommon complication of CAR T-cell therapy, where to get around that, we've given patients a dose of stem cells. For a lot of myeloma patients, we have stem cells stored from their prior stem cell transplants, and we can do that, and it has been effective.

I have not heard of any cases of such severe suppression of blood counts with teclistamab. That's probably because unlike with CAR T-cells, with teclistamab, if you get really severe side effects, you can just pause the medication and give things some time to recover. Whereas, CAR T-cells, this is both good and bad, they can maybe generate more intense activity in the body. It's a little bit less easy to control because you put the CAR T-cells in, and they're going to do what they're going to do. It's a little bit different from patient to patient.

With bispecific antibodies, because they're continuously dosed, you can always just pause the bispecific antibody if you develop a significant low blood count. That's what was done on the clinical trials. There were rules in place to -- if you saw a low blood count of a certain severity, you pause the medication, wait a week or two for it to recover, maybe give some Neupogen, et cetera, and then resume it once the blood count got a little bit better. All of those guidelines are in the prescribing information that that physicians can use that gives instructions basically on how to manage some of the side effects.

Jenny: Wonderful. Now, can we talk about just practicality of obtaining the therapy? If I go to my doctor and they say, yes, you qualify to receive this therapy. This is a good option for me. When you talk about the hospitalization for those first few doses, if you're going to a local provider versus an academic center that might have a little more experience with that, can the local provider do all of that or do you need to go to like a myeloma academic center for a couple days and then get your subsequent shots through your local provider? How are you managing that? How does that work?

Dr. Garfall: This is what we'll have to figure out as we get started with it. We haven't given it to anybody yet outside the clinical trial. There's always this delay between when a medication is approved and when we can actually start using it, because it has to go through some institutional processes, and suppliers have to figure out how to ship the medication, and all those things. With this medication, the FDA has instituted what's called a REMS program, which is a requirement that places that are going to administer the medication have gone through some very basic training about how to manage some of these side effects and some of the particulars about the dosing that I just mentioned, how to give the different step-up doses, how to manage the CRS and neurotoxicity.

It's a very simple process. But still, it requires a little bit of institutional initiative to get everybody who's going to be taking care of the patients certified in this program. We had a senator that takes care of lots of multiple myeloma patients, our pharmacists and hospital were all ready to go with it and are going through that process now. But a site that doesn't take care of as many multiple myeloma patients or maybe an oncology practice that is not as closely tied to a hospital as a big academic center, which is all under one umbrella, that might take a little time for those places to learn about the medication and go through the process of getting started with it.

In addition, you really need to think about some of the expertise necessary to manage the cytokine release syndrome and how a particular place is set up to do those inpatient doses, depending on how closely tied the oncology practice is to a community hospital. I really do think it's within the capability of any hospital and oncology practice partnership to administer this medication, but it will probably take a little bit of time until places are comfortable with it across these different care settings between big academic centers and community centers.

I imagine in our own practice network that the way this will get started is that patients will probably come down to our center to get started on the medication and get through those for the first month or two. Then, patients will then want to return to a practice closer to home to continue the medication. That's a much simpler thing to do. Because like I said, the risks of those toxicities are most significant in the early dosing. That process is transitioning a patient who was already stable on the medication and responding back to a local practice might give some of those local practices some initial familiarity with the medication before they want to bite off the early dosing. Maybe as a next step, they'll try and start the medication on some patients once they have everything set up with their hospitals to be able to give it.

Jenny: Well, I'm sure that process will get worked out, because I know patients are excited about receiving this therapy. I noticed therapy had really good overall response rates, and it's an off the shelf product in terms of getting like a very strong BCMA directed therapy, and effective therapy, it's really good. I just wanted to ask if the myeloma genetics matter, because I know in the past, we were all talking about precision medicine and maybe targeting all these genetic therapies, but CAR T and bispecific antibodies don't really do that. They seem to be working well for all patients across the board. Do you have any comments about genetic features in terms of the bispecific antibodies?

Dr. Garfall: Yes. It does seem like the targets of the bispecific antibodies like BCMA, and then there's a couple other ones coming down the pike that target other molecules on the surface of myeloma cells, they seem to be pretty widely expressed across all multiple myelomas. Not a guarantee in any given case, but it's not as though we know that there's a certain genetic marker that means your myeloma is not going to express this target.

What we have learned -- and this is really been reported in a couple cases of patients who have received CAR T-cells -- that after exposure to one of these therapies that targets a BCMA, it's possible for the multiple myeloma, that eventually progresses on this therapy, to have last expression of BCMA. That patient will then have a BCMA negative multiple myeloma, and will probably not respond to another therapy that targets BCMA, at least at that time. Now, who knows how that could change over time? Could the BCMA comeback? There's all these complicated genetics underlying these shifts in BCMA expression or loss of BCMA. That's just going to have to be figured out over time.

That's not the typical way we think about genetics and multiple myeloma. We're talking about different cytogenetic translocations and deletion 17p and +1q, all those different genetic subtypes of multiple myeloma, but it is speaking to profiling individual patients' multiple myelomas to see if they still expressed the target of the drug. It's going to take a while for us to figure that out. It's not perfectly straightforward, how to test multiple myelomas for expression of these different targets. Perhaps, there's just a tiny amount of the target there that your tests can't detect, but that's enough that the drugs can recognize it. We have to be careful about how we use some of those tests, and it's going to take a little while to figure that out.

Jenny: Definitely. I mean, that's the whole sequencing question that you're talking about. It's an important one for patients like, do I need to jump to a different -- because there are bispecific antibodies targeting different like GPRC5D, the other one that starts with an F that I can never remember.

Dr. Garfall: Exactly. FcRH5.

Jenny: Yes. You could go to a different target, and what you're saying is you might be able to come back to a BCMA therapy after the fact and maybe use something else for a year or something, or a few months, or whatever, and then come back. But I think that's the question for patients. If you have patients come in, now that there's this off the shelf option, and there's the CAR T option, and there's the antibody drug conjugate option, what do you tell your patients about what do you pick and when? I know it's a very complicated question.

Dr. Garfall: It is. No, this is where every patient's situation is different. This is why we have conversations with our patients and think about their particular circumstances as we sort these things out. I would say, some very rough guideposts. In terms of CAR T-cells versus bispecific antibodies, there's still really limited availability of CAR T-cells, both in terms of what centers are equipped to administer them and how close patients live to those centers. Also, even at centers that are equipped for CAR T-cells like ours, how many slots we have available for patients to manufacture. In addition to that, there's the time it takes to manufacture the cells.

There are some patients who really need something urgently for their myeloma. Waiting around for a CAR T-cell slot, and then getting that slot, and waiting around for the CAR T-cells to be manufactured, it's just not going to get that patient effective therapy fast enough. that's the patient that to me, that the bispecific antibodies make a lot of sense because they're very effective and they can be started right away.

On the other hand, even some patients with advanced multiple myeloma, meaning that they've had a lot of prior therapy, sometimes that myeloma is still under quite good control, and the patients are not actively sick with the multiple myeloma, maybe they're on a regimen, a combination regimen, and the disease is just starting to progress, the M spike is reappearing and increasing gradually, but they're not actively sick with multiple myeloma, that might be a good patient to wait around for a CAR T-cell slot. The advantage of the CAR T-cells is that it's a one-time therapy that you get it and you don't have to be on therapy, hopefully if it works for a long time after that. There's some real advantage to that.

We also don't necessarily have to think about it as either or. My goal with my multiple myeloma patients is to give them a shot at every effect of multiple myeloma therapy. It's not necessarily bispecifics or CAR T-cells, it might be bispecifics, and then CAR T-cells later, or CAR T-cells now and bispecifics later. The way that we've made progress for multiple myeloma patients over the last couple of decades, is by just making more and more treatment options available, allowing patients an opportunity to try more and more therapies, and that has extended survival for longer and longer periods of time.

To the extent that we know about sequencing, I think it's probably less important than just trying everything at some point. The sequencing, it really comes down to strategizing a bit about patient's particular situation. When do they need responses more urgently? When can they wait? What's the safest thing at this point versus -- and you can just imagine, there's so many different situations that can come up when you have all the different variables in the air. Patient preference matters a lot too. Actually, it matters a ton. Some patients really want that one time therapy so that they can maybe be off therapy for a long time. Other patients really want something right now. The complexity of CAR T-cells is daunting to them or just undesirable for some reason. It's amazing to be able to have these options to pick from. I think patient preference should play a big role on some of these decisions.

Jenny: Well, I know. kudos to these companies who are developing these products that we can have the option. I mean, how amazing is that? I just think what's happening in myeloma is just so incredible. I'm really grateful that we even have these. This is not a problem. I mean, it's a good problem to have, and some multiple things to choose from.

Dr. Garfall: I agree. It's been amazing. I've been practicing myself since 2014. it's just amazing. I sometimes give a talk to our fellows about multiple myeloma therapy, and I put up on a screen all the medications that are not FDA approved for multiple myeloma. It's amazing how the majority of them are not even approved when I started practicing just a little under ten years ago. My mentor, Edward Stadtmauer, who's the leader of our program here, I remember working with him as a fellow and in a research project reading over some of his clinic notes from when he was treating patients back in the early 2000s. It's just staggering, the different options we have. There was a lot of high dose dexamethasone and melphalan pills going on in those days, and it's just amazing how much progress has been made.

I really do have to be careful about this. Like I said, all this really has to be confirmed in those comparative studies. But we do get the sense that with this new suite of therapies coming online, these CAR T-cells and bispecific antibodies, there's real potential to add years to the expected survival of multiple myeloma patients. I'm hoping someday, we can get to where we're talking about a cure for some patients. I would say, we were maybe surprised we're hoping with CAR T-cells that we would see a large portion of patients cured as we do with some leukemia and lymphoma, that hasn't turned out to be the case. But maybe there is some portion of patients that are cured or maybe we can figure out the right combination of these potent therapies plus some of the older therapies that we can get reliably to cure our patients.

Jenny: We're all hoping for that. Thank you for all of your work. It's amazing. I have two more questions for you, and then I'm going to open it up for caller questions. If you have a question for Dr. Garfall, you can call 347-637-2631 and press 1 on your keypad. But my question is, the immune system, like you talked about the innate immune system versus the adaptive immune system at the beginning of the show. When you look at these immunotherapies, are there other markers that you are watching? Do we need to start watching for CD4 counts? I don't even know what else they are, to determine this myeloma specific immunity, or how the immune system is responding or not responding? Do you have other markers that you look at on a regular basis that we should all start looking at?

Dr. Garfall: Nothing that's really ready to start being used clinically. We and many other groups in in the myeloma research community are trying to examine our patients who have received some of these novel therapies, and look at who does well, and who doesn't do as well, and try to understand what in the immune system makes the difference between a responder and a non-responder, or a long-term responder and a short-term responder. Increasingly, there are some really fancy tools available to us on the research side, the ability to take a bone marrow sample and look at the entire gene expression program of every individual cell on that bone marrow, myeloma cells, T-cells, B-cells, dendritic cells, all the different cell types that make up the bone marrow, we can look at each one individually, and see how their gene expression program differs between patients in different groups that have response.

I think that will generate a lot of new ideas about how to improve these therapies going forward, but I don't think any of those results are, are kind of validated yet or ready to be used in monitoring individual patients right now. It's still in the idea generation phase, but I think we will get to the point where we can perhaps have some features that we look for and we say, okay, CAR T-cells are better for this person, bispecifics are better for this person, antibody drug conjugates are better for this person, based on various aspects of their immune profile.

Jenny: Yes, or when's the best time? When is my immune system the strongest to be able to have these therapies be the most effective? I think, patients would love to know that. I'm sure you would too.

Dr. Garfall: For sure, for sure. And what therapies should we avoid that can beat up the immune system before we use some of the immune therapy. That's an area. It's a really active study.

Jenny: Right. Absolutely. Well, I'm just going to jump to call our questions. Go ahead with your question.

Caller: Okay. A little bit more on the antigens, these targets for the drug. I'm pretty puzzled. Am I correct in assuming that if you find an antigen that is present only on all the cancer cells, and on no normal cell, you would have in a sense the perfect drug? I'm confused by -- you seem to say that, like say, BCMA comes and goes on the cancer strain. How much of this BCMA is on the normal cells? Because I mean, it seems to me if you only have 2% of cancer in your plasma, you can't have much more than 2% of the BCMA on the good plasma cells. Otherwise, you'd be getting a lot of side effects. What determines when the BCMA appears and doesn't appear on both normal and cancer cells? If I could ask you a simple question, a second question, among the side effects, is there known taste disturbances among the side effects? All right. Thank you.

Jenny: Great question. Thanks.

Dr. Garfall: Yes, great question. I'll start with the second one, which is a little simpler. To my knowledge, teclistamab does not cause any disturbances in taste. That is an issue that has been seen with a drug called talquetamab, which is another bispecific antibody that targets not BCMA but a protein called GPRC5D, but we haven't seen that with teclistamab to my knowledge.

You're right that a perfect immunotherapy target will be present only on cancer cells and no other cells in the body. I'm not aware of any perfect immunotherapy target. I think all of them have some risk of expression on certain normal cells. In the case of BCMA, the main normal cell that we worry about is the normal plasma cells. Remember, myeloma is a cancer of plasma cells, but there are also normal plasma cells that are not cancerous in the immune system. Those plasma cells will express BCMA and will be targeted by BCMA targeted therapies like teclistamab.

What I was referring to in terms of expression of BCMA on multiple myeloma cells, yes, that can vary between patients in terms of how much BCMA is on each myeloma cell, what percentage of the myeloma cells express BCMA. We've seen that that can even change a little bit in response to therapy. Patients who receive CAR T-cells targeting BCMA, the residual myeloma cells that aren't killed by the CAR T-cells, those cells will have less BCMA on them. But then, as those cells grow, the BCMA levels may go back up on them. There's a dynamic aspect to BCMA expression on multiple myeloma cells that may affect how well certain immunotherapies work.

There are also some tricks that have been developed to try and increase the amount of BCMA on myeloma cells. There's a type of drug called a gamma secretase inhibitor, which is an oral medication. That seems to dramatically increase the amount of BCMA on multiple myeloma cells. There are clinical trials going on combining gamma secretase inhibitors with different immunotherapies that target BCMA. I hope that answers your question, although I admit it is a little confusing, and we're still figuring out what makes BCMA go up and down, what makes it go permanently go away, versus just transiently go away on multiple myeloma cells, and how that should affect the likelihood of patients responding to different therapies.

Jenny: Okay, great question and great answer. Thank you so much. Next caller, go ahead with your question.

Caller: Doctor, I appreciate your time. I have a couple of related questions here. The first is, are there any clinical trials in the works that are looking at teclistamab being moved up more to a maintenance setting in the U.S.? The related question is, whether you're expecting maybe the side effects to be impacting patients who are getting treatment with teclistamab earlier in the disease course, that they're going to be different than those who are getting it later in the disease course.

Dr. Garfall: Sure. Just to clarify your question about the maintenance, do you mean using teclistamab as a post-transplant maintenance or do you mean just once you get started on teclistamab, adjusting to a lower intensity maintenance schedule?

Caller: Post-transplant.

Dr. Garfall: Got it. Both are good questions. I have heard about some trials in the work testing to teclistamab in -- actually no, I think actually, it's already open in Europe. I believe there is a study being run in the European Myeloma Network that is testing teclistamab as a post-transplant maintenance therapy either alone, I think, or in combination with lenalidomide. Don't quote me on this because I'm just remembering this. I don't have it in front of me. I believe that is being tested in a trial in Europe in a group of European centers called the European Myeloma Network. I suspect there'll be other studies like that popping up, because there are now studies testing daratumumab as a post-transplant maintenance. Forgive me. I'm having trouble remembering the other question you asked. I'm sorry.

Caller: The profile of side effects whether it's different whether they get it early or late.

Dr. Garfall: Sure. I think where you could have issues using it in earlier lines of myeloma therapy is that patients may just be on it for a much longer period of time. Even using teclistamab and drugs like it in the relapse setting, as was done in these clinical trials, we've had some patients who have been on the drug for years. Some patients who progressed earlier, and as I mentioned, at 12 months after starting treatment, the patients who are responding, about 70% are still on therapy, but 30% has progressed. I think that immune suppression is going to be cumulative. The longer you're on an immunosuppressive medication, the more time you have to develop severe infections. I can imagine that in trials that are ongoing testing teclistamab earlier on, it's possible, it's such a potent therapy.

Even with standard myeloma therapy, first- or second-line therapy can go on for years. If you throw in an even more potent therapy, that first- or second-line of therapy could last for many, many years. That's a long time to be immunosuppressed. I think we could see, just numerically, more infections accumulate in those patients and if they're on it continuously. At some point, could you imagine that that starts to outweigh the benefit of the teclistamab used early on, because some of the other myeloma medications are also very effective early on. That's what these big clinical trials are designed to figure out. It's going to take some time to see how that sorts out. Like I said, there are some preventative measures we can take for infections, but I think that would be one side effect that we're a little bit more about using teclistamab early on.

I'll add that I think it will be interesting over time to test interruptions of therapy with this class of medications. Perhaps, that's the right balance for patients who are getting teclistamab early on, is that they might not stay on it forever and ever the way we do with our typical maintenance therapies. But again, that's a question that really has to be sorted out with clinical trials to figure out if that's a better strategy or a safer strategy than continuous dosing.

Jenny: Okay, great. Thank you so much for your question. Dr. Garfall, do you have a minute for a couple more questions?

Dr. Garfall:  I do.

Jenny: I know we're over time. Okay.

Dr. Garfall: I'm okay.

Jenny: Okay. Next caller, go ahead with your question.

Caller: Yes. My question is whether there was a higher incidence of neuropathy with the drugs? Also, I was under the impression that just like with a CAR T-cell procedure that you had to get some heavy drugs upfront before you could start. Do you have to get some drugs that suppress things or whatever, like you do with the bone marrow transplant and the other things before you can start teclistamab?

Dr. Garfall: Those are good questions. First, to my knowledge, peripheral neuropathy. When I think of neuropathy, I think of the numbness, and tingling, and pain in the hands and feet that can happen with, for example, Velcade therapy. To my knowledge, that was not a side effect that was observed, at least not many patients with teclistamab. There were other neurologic issues, like I mentioned, the occasional patient who had that ICANS, the brain dysfunction that can happen with those initial couple of doses. Then, that one instance of Guillain-Barré Syndrome. But the conventional neuropathy, I don't think was seen, at least not many patients.

The question about what we might call conditioning chemotherapy, or lymphodepleting chemotherapy, no, that's not required for teclistamab. That's actually another important difference with CAR T-cells. With CAR T-cells, in order to get the CAR T-cells to grow inside the body and activate inside the body, before you give CAR T-cells, you need to give a little bit of medium intensity chemotherapy, usually with two chemotherapies is called Cytoxan and fludarabine. That kills off some of the normal T-cells in the body, so the body starts producing chemicals called cytokines that help T-cells grow. Then, once those cytokines are being produced after the chemotherapy, you can insert the CAR T-cells, and then those CAR T-cells will grow in the body. That doesn't seem to be required for the effective bispecific antibody. Patients didn't require any pretreatment with chemotherapy or anything. They did get some dexamethasone just before the first couple of doses of the medication, but no other significant pretreatment.

Caller: Thank you.

Jenny: Great. Good questions. Okay, last question. Caller, go ahead with your question.

Caller: Yes, two sub questions. Do all normal plasma cells have BCMA? secondly, is the reason why the drug increases the chances of infections because it kills the normal cells that produce the immunoglobulins and other things that our immune system needs? Thank you.

Dr. Garfall: Sure. I would say that the vast majority of plasma cells express BCMA. I can't say for sure that there's not some subset of plasma cells that maybe don't, but I would think of BCMA as being a cardinal feature of plasma cells. BCMA targeted therapies would be expected to kill the majority of plasma cells, at least in the bone marrow.

In terms of what causes the increased risk of infection, I don't think we 100% know for sure, but our strong sense is that the depletion of the normal plasma cells that make antibodies is a big part of it. The loss of antibody production is a big part of it. But it's probably not the whole story, because we can give antibody replacement therapy through intravenous immune globulin, but patients still had some difficulty with infection. There may be some other immunosuppressive properties of the drug through different mechanisms that we don't totally appreciate yet.

Jenny: Okay, great. My last question would be, do you need a caregiver to get the therapy?

Dr. Garfall: Oh, that's a good question. I would say it's not like CAR T-cells where you're told that you have to stay close to the CAR T-cell center for 28 days, and can't drive, and things like that. I want to be careful what I say because I'm not 100% sure that there's not some language in the describing information that speaks to this, but what I'm comfortable saying is that patients who are on this therapy for a long time, they have quite normal quality of life. They don't have a lot, or maybe even any cumulative toxic. The risk of infection, more of a risk, but in the absence of infection, patients don't feel a lot of side effects from ongoing therapy even for a very long time. They certainly don't need any extra caregivers in the stable phase of therapy.

I think it makes a lot of sense. Anytime somebody is starting a new myeloma therapy to have a little bit of support, as I mentioned, in the first few weeks of therapy, there can be some low blood counts or requirements for transfusions. I've also just seen patients get a little bit tired during that time. The way I've made sense of that is that thinking the immune system is very active in the body fighting myeloma, and that you can imagine creating some fatigue in those first few weeks. It might not be a bad idea to have some extra support in getting to and from the hospital in those initial doses. But whether there's an absolute requirement for it in the REMS program or the prescribing information, I have to double check. I'm sorry. I don't have that at hand.

Jenny: No, that's okay. You would think it'd be a lot less compared to CAR T, it sounds like it, because you're not getting all the preconditioning, you're watching for lower-level symptoms typically.

Dr. Garfall, you have been amazing. Thank you so much for doing this with us, and for staying over time, and answering all our questions. We really appreciate your work in helping move the therapy forward through the process and getting it out into the myeloma clinic. We're just appreciative for everything you're doing in the CAR T space, in the bispecific space. It's truly terrific.

Dr. Garfall: Thank you so much. It was a real honor and pleasure to be here. Thanks to you and HealthTree for all the wonderful support and information you provide to our patients.

Jenny: Well, thank you so much. Thank you for our listeners for listening to the HealthTree Podcast for Multiple Myeloma. We invite you to join us next time to learn more about what's happening in myeloma research and what it means for you.

---

We appreciate your donations to support the HealthTree Foundation Podcast.

DONATE