to questions and answers, and I'm looking forward to it. Today's topic, as I mentioned, is infection prevention for multiple myeloma patients. Myeloma patients need to be vigilant due to their immunocompromised status. After fighting myeloma and achieving remission, many patients continue to worry about other infections or diseases that might come their way, and I'll even add, those who are inactive treatment also carry this worry. What steps should be taken to prevent infection, especially in today's COVID, post-COVID unknown world, and how can patients enjoy a high quality of life while still being cautious or protective? Here today to speak to us on that point is Dr. Dermin. It's my pleasure to introduce him to you. He specializes in hematology and oncology, is an expert in multiple myeloma and other plasma cell disorders, such as monoclonal gammopathy, amyloidosis, plasma cytoma, and poem syndrome. He also diagnoses and treats cancerous conditions and uses the most innovative techniques like CAR-T cell therapy and stem cell transplant in order to deliver long-term success to his patients. Along with clinical practice, Dr. Dermin remains committed to research and is focused on identifying strategies that can lead to a possible cure in myeloma, including using very sensitive tests to detect minimal residual disease. This is the MRD test that you've probably heard of. And Dr. Dermin is also investigating new methods and therapies designed to improve outcomes and quality of life for his patients. He's interested in evaluating reasons for racial disparities in multiple myeloma and to better understand and care for these patients who are affected by those disparities. And his work has been published in several peer-reviewed journals, including the Journal of Immunotherapy of Cancer, Blood, Blood Advances, Blood Cancer Journal, Leukemia and Lymphoma, and British Journal of Hematology. Dr. Dermin, we're really excited for your presentation today, and the time is now yours. Thank you so much, Audrey. And thank you to all of you who have tuned in. I really appreciate it. And I'm gonna make sure we have plenty of time for questions. I've learned over the years, myeloma patients are the savviest patients out there. So keep the questions coming. I'm going to address, I will address all of them at the end. I think that will just be best. And I promise I'll kind of limit my slides to maybe 25 to 30 minutes, cover what I think are some of the most important issues, and then we'll have plenty of time to address all of your questions. And maybe I'll bring up some more as we go along. As Audrey said, my name is Ben Dermin. I'm an assistant professor at the University of Chicago. I specialize in multiple myeloma. And this is a topic that is super, super important. And I'm going to talk about multiple myeloma and infection prevention. And briefly, just before I start, here are some of my disclosures. I don't believe that these would affect the content of our presentation, but I want to provide those regardless. Okay, so what are we going to talk about? We're going to talk about why multiple myeloma causes infections. Seems simple, but I think it's important. And then discuss which infections we need to be paying attention to. Take on to really try to prevent this. What are the things that might be manageable or avoidable? All right, you guys are a savvy group, but it's important to understand what myeloma is, first of all, so that we can then understand why things go awry with infections, right? So this is a blood cancer that's derived from plasma cells in the bone marrow, and plasma cells are actually normal to have. We all have them, right? Healthy and those with myeloma. They make antibodies, which are extremely, extremely important, right? So you'll see antibodies, you'll see immunoglobulins, same thing, right? But cancerous plasma cells, such as in myeloma or amyloid or other related disorders, can accumulate in the marrow, in that manufacturing center of all your blood cells. And now they start to secrete excess antibodies that we call monoclonal antibodies, because they're all identical. They're all from that same clone, and they really have no useful purpose, right? So you can see the antibody here on the right, it's a Y-shaped protein, you've got your light chain on the end, and then you've got the heavy chain, which is the long arm here. And this is what we call an intact immunoglobulin. And let's put aside the fact that some patients will only make this light chain piece or the only part that's detectable, but that's the idea, right? All right, but patients with myeloma are seven times more likely to get infections, so much higher risk of infections. And part of the reason is because you have much lower normal amounts of immunoglobulins or antibodies, the healthy normal stuff that you're supposed to make is not being made because you have all of these other plasma cells that are making these dummy ones. We also know that there's lower lymphocyte levels in myeloma patients and typically lower numbers of neutrophils, which are sort of your first line of defense as part of white blood cells. There's also increase in what are called cytokines, which essentially are chemical messengers. And one of the things that has been shown is that it can actually inhibit another type of lymphocyte called T cells that are very important for immune system, both infections and other offending agents in the blood, but helper T cells can be inhibited by these cytokines. So why are antibodies so important? Because that seems to be a real big piece to this. Well, antibodies are capable of locating and attacking foreign proteins or what we call antigens, so antibody, antigen. And there's different flavors of antibodies. You're probably familiar with this because for those who get their blood tested a lot, you'll see their IgA or IgG or IgM level. So IgM is one of the first antibodies that comes on the scene. It's a first responder sort of thing, but they have a short lifespan. So they don't really last a long period of time. IgG is one of the most important ones and certainly the most prevalent. So if you've ever looked at an IgG level, you'll notice that that one's usually always the highest. And these are sort of memory antibodies. Those are the ones that are persistent, that are made continuously. They're made to provide protection against whatever antigen it was made to be against. And these are really the workhorse for fighting infections. IgA is an interesting one because it's really predominantly found in the linings of the GI tract, the lungs, even the genitourinary tract, like the bladder, the urethra, et cetera. And so they really are almost like a first line of defense because these are there to sort of help against offending agents that might be in the GI tract, which really exposes us to the outside world, anything we put in our mouths. And then IgE is not really relevant to today, but these are what's stimulated by allergens. So my IgE levels are probably through the roof lately because it's spring and my eyes are watering like crazy from all the pollen in the air. So why are antibodies important? Well, this is why, right? So how do they work? So it does something predominantly this process called opsonization and phagocytosis. That's a mouthful. Basically what you're doing is antibodies are labeling certain antigens or offending proteins in the body as foreign. And what then happens is it recruits cells, it's usually called macrophages to go and just eat these things up, right? And that's how you fight infections, right? Is that you have these antibodies, they label these things for destruction and then you get destruction. There is another pathway that antibodies can lead to cell death, which is called a complement mediated pathway. It's less important, I would say, for antibody, for infection prevention, but can be another way that in which an infected cell, for instance, can be told to just essentially die because you have this complement process that leads to chemical pathways that lead to the cell to destroy itself essentially. So what happens in myeloma? Well, okay, so you have myeloma where you're not making as many antibodies or good antibodies, healthy antibodies, normal antibodies. And then we take treatments in myeloma that are designed to kill plasma cells because that's the problem here. Well, you might actually end up killing some bystander good plasma cells, in which case both of these things conspire to really decrease antibody production. What you're looking at here on the bottom is the various immunotherapies that we have that have been so helpful in myeloma, but they do run the risk of not only killing myeloma cells, but other cells as well, right? Other immune cells, in particular plasma cells that may have similar processes to the myeloma cells. So we worry about bone disease, we worry about kidney damage, we worry about anemia in myeloma because those are the things that people typically present with. But infection is actually the leading cause of death in myeloma. It's easy to lose sight of that, right? In fact, the first two to three months on treatment from diagnosis is really when patients are at the highest risk of death. In fact, if you look at all early deaths in myeloma, it's not from the disease rapidly progressing or a fracture that leads to something bad happening. Most deaths, almost half, are from infection. So the other important thing is that the more amount of myeloma that's present, which we call a tumor burden, the higher the risk there is. And the longer that people are living, the more treatments that have been given leads to this accumulation of suppression of the immune system. So of all the things that are kind of intuitive, the longer that people are alive, the more that their immune system may be suppressed. And that's becoming increasingly true with CAR T therapy, these new immune therapies that I just mentioned on the last slide. So these are things that we have to be mindful of. So, okay, so we've kind of set the groundwork for why infections are more common and why it's important to address this in myeloma. But let's talk about the ones that are relevant, right? Because it's not just every single bacteria or virus in the world. So here are the list of the things that we're gonna discuss, and I'm gonna kind of hit some of these in more detail. So let's talk about shingles. This is probably the one that happens the most. And what's interesting is that myeloma itself probably doesn't increase the risk for shingles that much. What does though are a lot of our treatments, and I see there's a typo, it should be exasimib here, but proteasome inhibitors, bortezomib, carfilizomib, exasimib, definitely increase the risk of all herpes viruses, but in particular shingles. And it's about 2.5, 2.6 to be exact, higher risk with one of these proteasome inhibitors compared to just dexamethasone alone. Now, interestingly, in preparing this talk, I always assumed that there was a higher risk for cold sores, which we call herpes simplex, but actually that doesn't really bear out. So that's just an interesting piece to it. Certainly shingles is, I think, worse than cold sores. But when you're thinking about whether I might have shingles or not, this is kind of a classic presentation, but it's a linear, what we call dermatomal. It follows the dermatome where the nerve endings run, and it's painful, very painful, itchy rash, usually with fluid-filled vesicles. But then as time goes on, those vesicles pop and it kind of scabs over. Highly contagious, actually, during the vesicle phase, that fluid is highly contagious. So if you're around people of childbearing age, especially if they're pregnant, that's something you really wanna make sure that's covered up and not exposed to. It's not something that pregnant people really should be exposed to at all. But shingles is obviously a major one. Okay, bacterial and upper respiratory infections. I kind of lump these together. So as far as bacteria, it's often the common bugs that we see. This strep pneumoniae, staph aureus, E. coli, and other bugs that we see usually in the GI tract. So these are the ones that we look out for. Viruses, before COVID, it was a lot of the run-of-the-mill stuff, rhinovirus, respiratory syncytial virus called RSV, human metanumovirus, which was circulating earlier this year in Chicago among our patients, non-COVID coronaviruses, and influenza. Before COVID, these were the things that we were really worried about. And for the most part, these have a predilection for affecting the lungs. So we were seeing mostly pneumonias. We weren't seeing as much urinary tract infections or cellulitis or even GI tract infections. For the most part, we're talking about pneumonias. CMV is another one that is less commonly looked at, probably less of a concern for patients who have not been exposed to CAR-T therapy. But there's definitely something about the chemotherapy, what we call the lympho depletion for CAR-T and CAR-T itself that leads to reactivation of CMV. We've also seen it occasionally in patients after stem cell transplantation. But the reason this is important is that most of us on this call have been exposed to CMV, have been infected by it. And it's usually a pretty mild virus, usually contracted in childhood, but it never really goes away. So similar to like shingles, if you've had chickenpox, it lies dormant until maybe something suppresses your immune system. And so this is actually from a study that was done in CAR-T patients. And they found that about 10% of patients actually had reactivation of their CMV after CAR-T. And you're not gonna find this unless you look for it. So it's something that has to be monitored. So for those of you who have received CAR-T or are going to or thinking about that, this is something that you wanna make sure, your physician or your providers are keeping in mind. Okay, got to talk about COVID, right? And what would it talk be if we didn't talk about COVID? You're talking about it since 2020, I gotta keep updating this slide probably to change the zero at the end to whatever year we're in, but it does feel like it's been a dumpster fire since the very beginning. And what do we know about COVID and myeloma? Well, this is the latest and I'm sure it's gonna change the second I finish this, but we have about a two times higher risk of COVID in patients with myeloma compared to the background population. Just over half of myeloma patients have what we call neutralizing antibodies to COVID after the first vaccination. Neutralizing antibodies are what we think is the amount of antibodies and the type of antibodies that are required to really develop an immune response if you were to be exposed to COVID. But that's only after one vaccination. After two vaccinations, the great majority of patients have detectable antibodies, but about 16% actually had undetectable antibodies against COVID after their initial two vaccine series. And we don't know what's gonna happen with boosters. And now the CDC, the latest is that the initial vaccine series is three shots with two boosters. So a total of five shots overall, but many of you, if you were vaccinated at the beginning, you probably got a two vaccine series and then boosters after that. But what we see is especially this lower level of antibody detection in patients who've gotten things like daratumumab or esotuxumab, which are considered anti-CD38 antibodies and also anti-BCMA therapies. That's CAR-T, that's belantumab, methadone, that is certain bispecific antibodies that are under investigation if it was part of a clinical trial. So these are the patients who are typically not developing antibodies. For those who've ever been on benetoclax, that's another one that we've seen, at least in the CLL literature and anecdotally among my patients where I see very little antibody production as well. So I wanted to spend the rest of the time just talking about recommendations for prevention of infections. And I broke it down sort of by the setting of treatment because you all may be in different points in your treatment or have had different things and you kind of have to tailor it a little bit based on where you're at. Let's talk about newly diagnosed patients. So I already mentioned that the highest risk of early death is infections. It's usually in the first two to three months. So this was a really cool study that was done in Britain. It was called the TEAM trial in the UK to be exact. And what they did is they randomized patients, a large number of patients, almost a thousand patients to get an antibiotic called levofloxacin, AKA Lavaquin, or nothing, placebo. And over the first three months, what you're looking at here is the number of episodes of fever, which they thought was a surrogate for infection or death, okay? And what they saw is that Lavaquin or levofloxacin actually lowered the rates of fevers, infections, and death in the first three months. Not any other new treatments. This is people who are already being treated for myeloma, but when they introduced levofloxacin, they actually lowered the mortality rate for patients. That's pretty special. But the other thing that patients may be on, is Bactrim, which is trimethoprim sulfamethoxazole. If you can say that 10 times fast, you get a gold star. So Bactrim actually wasn't intended to be studied in this trial, but of course, there were some patients who were on it. And it did seem to be associated with better survival as well. Now it wasn't studied with the same rigor as levofloxacin here. But the thing is Bactrim had some effects that couldn't be attributed just to preventing something called pneumocystis geravici or carini pneumonia, which is the reason that we usually give it. It probably had some other antibacterial properties to it because we didn't really see lower incidence of PJP, PCP in patients who got Bactrim. So this is an interesting study. You'd think that this would have just caused everyone to start using levofloxacin, but even I myself don't routinely use this. I can explain a little bit my reasoning for that. So when I have people in induction therapy, newly diagnosed, I recognize that the first three months are the highest risk. All of my patients get shingles prophylaxis. Prophylaxis means protection. So what I recommend is cyclavir. And that's like a absolute 100% all the time, never miss it. I do acyclovir. Some people may be on valacyclovir. There's no difference. As long as you're on some kind of anti-shingles protection, that's fine. For antibacterial prophylaxis, as I just mentioned, I don't routinely use levofloxacin or Bactrim for that matter. I do if patients are already having low neutrophil counts, low white blood cell counts to begin with, or if when I do the bone marrow, I see lots and lots of plasma cells taking up almost the entire bone marrow, I suspect that they will have a period of neutropenia, low neutrophils. So I usually will give about a month or two of that until I get them through the initial stage. And then I stop. Anti-PCP, which stands for this pneumocystis carinae pneumonia. I don't usually use Bactrim. If I do, it's going to be either three times a week, Monday, Wednesday, Friday, or twice a week on Saturday, Sunday is our technique. It probably has very few side effects. So it's kind of a low priority, but low risk as well. And then for hepatitis B, if for some reason, I know that some patient has hepatitis B or has been exposed to hepatitis B, I will typically start a drug called Entecavir to prevent that. That's, I would say, less common overall. Okay, what about after transplant? Transplant is really involving this high dose of melphalan. And melphalan is unique because it really wipes out the immunity of a patient. It basically erases all of your immunity that you gained over the many years. And it ends up causing what's called lymphodepletion. So T cells, B cells, natural killer cells are all depressed. And as far as how we approach that, well, from the antibacterial standpoint, I will use levofloxacin here routinely until the neutrophils are back up above 1,000. For most patients, that's the time at which they're leaving the hospital from their transplant. Same with anti-fungus. So fluconazole, I will continue until neutrophils are back above 1,000. That's again, usually within a couple of weeks of the transplant. For antiviral, we are actually gonna be changing our standard. We have been using this higher dose of acyclovir for six months, but I don't think that really provides much benefit. As long as you're on some amount of acyclovir or valacyclovir, that's the most important. Hepatitis B is the same as I already mentioned. And Bactrim, I have actually started to use actually started to forgo Bactrim for most patients as the rates of pneumocystis are super, super low, even with or without prophylaxis. So I don't think that's so important. What is important is adhering to a vaccination schedule that your transplant doctor should have provided to have a revaccination schedule for you. That includes also a strategy for vaccinating, revaccinating against COVID. So the thing that's gonna be a little bit harder now is for those that have already gotten four shots of COVID or whatever with their two boosters and then go to transplant, how to vaccinate those patients, I would probably start over with a new series of vaccinations, but I'll go into a strategy about how we can think about that. After transplant is really a period where you're gonna have a high likelihood of infections or fevers. And it may not always be due to infection, the fevers that is, but certainly the most likely. So that's because the neutrophil counts are so low. The lymphocyte counts are so low. There's really no first line or second line of defense here. But the thing is, even when fevers come on, we only find an infection, so to speak, really the bug that's responsible about 50% of the time. So we often give antibiotics during that time, but we don't always know that it's going to lead to, that's actually treating an underlying infection. But we do it until the fevers go away to be safe. We'd hate to miss an infection. Okay, what about after CAR T cell therapy? That's another unique standpoint. A lot of these recommendations are the same actually. What I added here was about CMV, because for patients who have reactivation of CMV, whether it's low level or high level, you may want to be introducing a drug called valgancypivir, which is different than acypivir, but this helps to prevent or treat CMV. These actually have some side effects. In particular, they lower blood counts. So this has to be sort of balanced. It's definitely a balance in terms of drugs that will prevent CMV from going crazy, but also not lowering your blood counts. Talk to your doctor if this is an issue. There are some newer treatments out there. In particular, there's a newer one called maribivir, which doesn't cause as much of low blood counts, but can also treat CMV. And there is something called latermivir, which can help prevent CMV for patients who have a high risk of CMV. I'm not routinely doing using that post after CAR-T, but certainly valgancypivir at a lower dose versus a higher dose can be really helpful. Another common question I get from patients, should I get the shingles vaccine? And I sort of shrugged. And here's why I shrugged, because acypivir is cheap and has almost no side effects, if not none, and is over 90% effective. And Shingrix, which is the shingles vaccine that's inactivated and safe to give to even immunocompromised patients, is about 90% effective in immunocompetent patients and in patients without immune system issues, but is only about 70% effective in patients who underwent a transplant. So if you get Shingrix, I don't really think that means you can come off of acyclovir. So I often just say, look, I'd probably just stay on acyclovir. If you wanna get Shingrix, fine, but I think it's a little bit patient choice. So think about which one you would choose in this case. I often still recommend acyclovir alone. What about IVIG? So what's IVIG? These are infusions of intravenous antibodies, immunoglobulins, that are actually derived from many, many, many donors of plasma. The typical guidance has been, and many of you may have even received it, that we give IVIG when the corrected immunoglobulin G is less than 400. When I say corrected, I mean accounting for your M-spike. So if the M-spike is there, your IgG may actually be high, but it's not actually useful IgG. So you wanna subtract that out. The thing is, we've actually done research on this. I've done the annoying thing of citing my own article here, but we actually did this at our institution where we looked at just supplementing IVIG for less than 400, or for those who have less than 400 and a history of infections. And it's really those patients that seem to benefit more than the ones who just have a low 400. I have a patient in my panel who's got an IgG level of 50 or something like that. It might even be below the limit that we can detect. So, so low. I mean, I doubt anyone here has a level that low. And over two years has never developed an infection without IVIG. So it doesn't tell you the whole story, right? Just the IgG level. It happens to be that IVIG is on a national shortage, has been on a national shortage for a long time. So there have been some strategies to reduce the amount, but I think the supply has increased over the last year or so. All right, I wanted to end with COVID precautions. This is what I'm gonna call my May, 2022 edition. It could be different in June, but you know, so before transplant or CAR-T therapy, what I'm making sure for my patients is number one, have they had an adequate number of COVID vaccinations? The initial series plus two boosters, right? That's the recommendation right now. Secondly, Avuchel, which has got an impronounceable name. This is antibodies against COVID that can be injected into you. And I typically will give this to patients because I know that they're about to go into a therapy that's going to deprive them of, you know, antibody producing cells. So it makes sense to do that to provide them at least several months protection against COVID. You know, then the question is, should we be checking antibody levels against COVID? This is controversial. Most people say, don't do it. At least the CDC says, don't do it. And I personally like to. It helps me understand if somebody has actually responded to the vaccine, realizing that antibodies aren't the whole story. There's also other lymphocytes and other immune cells that are involved here. But you know, I find it helpful. And then I actually find it helpful to look after transplant or CAR-T because, you know, if the level of the antibody levels was high before your treatment, but now is low, well, okay, that means you probably responded and we can go and revaccinate you and get back to where we were. If it was low before transplant or CAR-T and now it's still low, well, sure, we can revaccinate, but Avuchel is going to be super important here to give you additional protection because I don't know that the vaccine is really doing a lot. And if I don't have the levels before, but I have them now and I see that the antibody levels are high, you know, you could consider actually just waiting to do any vaccinations because you have protection right now. It's not going to be that you can, you're probably not going to be helping yourself too much at the moment, might as well wait. And what about people who develop COVID or just have a positive test for mild symptoms? You know, there is outpatient therapies, there are outpatient therapies available. The newest one that still works against the Omicron variant is this drug called BebtilovaMab. It's an antibody therapy similar to Avuchel, but it's an intravenous therapy that is approved for, or at least has emergency use authorization by the FDA for treatment of patients with moderate to severe COVID. Paxlovid, you've probably heard in the news, is an oral drug, it's five, there's a combination of drugs, it's five days, it does have some interactions. We are also seeing rebound phenomenon where patients are completing a five-day course of Paxlovid and then COVID goes away. And then all of a sudden, a few days later, they feel just as sick as they did before. This is not the Paxlovid's fault, it's the fact that the virus still was present at the end of the five days and sort of just replicated and caused reinfection. This is happening to normal people without myeloma as well. Malnupiravir is also available. It's not as effective as the other two, but is another option and has fewer drug-drug interactions. It should not be given to those of child who are pregnant. The other thing is this. So if you give a monoclonal antibody like Abucheld or Bebtilova map, it actually is an IgG kappa antibody. So it will cause in some patients a spike on your M spike. And actually vaccination may lead to transient elevations in light chains. So it's important if you see a change in your parameters, it's not that your myeloma is going out of control, it may be just that you've gotten a monoclonal antibody or vaccination that's causing a change there. So just to wrap it up, patients with myeloma, we know are at high risk of infection, especially in the early months, those first three. And of course, after transplant and CAR T therapy. And a lot of this is due to decreased antibody production, but there's also other effects on the immune system. And as far as what can or should be done, I hope I've made the point that shingles protection is an absolute must for everyone. COVID protection is variable. There's probably no one size fits all approach, but talk to your doctor about what they recommend. And antibacterial protection also needs to be tailored, I think to each individual, but for the most part, it's not always required in my opinion. And for these other ones, CMV, pneumocystis, Stravichia or Carina pneumonia and hepatitis B, it really is gonna depend on your situation, probably more CMV for those who are after CAR T, hepatitis B for only those who are positive or have had a prior infection, not for those who've been vaccinated. And for pneumocystis, I think the days of us having to do that are probably numbered, but it's still hard to get rid of old habits. And again, it has very few side effects. So the risk benefit is such that it probably is useful. So, all right, I am going to stop sharing my screen and I see there's been lots and lots of questions and I see the number of participants increase since I started too. So if there are things that we missed. So, I don't know, Audrey, what do you think we should do? Should we just try to go one by one here and go in order, chronological order? Or what do you think? What should we, do you have some questions you wanna start with? Yeah, good question. I think we should start off with, I would say the elephant in the room, but the question of how can patients balance their quality of life with being preventative with infection? I mean, we hear every day, you know, patients saying, I have a cruise in September, is it safe to go? And these are good questions because their life is literally on the line here. So, how do you counsel your patients? Yeah, so there are, I think there are some things that we have to take into account. One is like, what would I have recommended before we had COVID, right? And then what do I recommend in the age of COVID where we're a lot more sensitive to these things? You know, what I try to divide things up for people is lower risk encounters, higher risk encounters, right? You know, I have some patients that are scared to even go to the grocery store. And, you know, part of what we're trying to do with our treatments is to actually help people's quality of life. And I can't say that I'm improving anybody's quality of life if I tell them they have to stay at home and never go out ever again, okay? But that also means that there is going to be a risk for infection. There's no way that we can reduce that risk to zero. I mean, honestly, I mean, just the way the world that we live in, it's not possible. So, lower risk encounters. You know, for me, if you're wearing a mask at the grocery store, you can go to the grocery store, you know, and you have to realize the whole world is moving on. They don't care about us. They don't care. They don't care that you're immunocompromised. And it sucks. It really does. I feel horrible for all of my patients and for anyone on this call who can relate. You know, I have two unvaccinated kids at home. They're not immunocompromised, unfortunately, as far as I know. But, you know, I also have to be mindful of what I do with them because, you know, they may or may not have been exposed to COVID. And, you know, even myself, you know, we can see that that risk is still there and the numbers have been increasing in Chicago even recently. So, but what it means is we have to figure out how can we manage and mitigate the risks that we have. So, okay, so here are my common sense things that I try to recommend. Number one, get a good fitting mask that you like. It can be disposable. I prefer KN95 or N95, you know. The KN95s, I think, are a lot cheaper, simpler. They work, I would say, pretty close to as well as an N95. But, you know, wearing surgical masks or cloth masks, we've pretty much seen that they're probably useless. So, and I'm telling my employees, you know, I shouldn't say my employees, my coworkers, who, you know, I work with and I'm like, you guys should all be wearing N95s in the hospital, even if it's not required. When you go for your doctor's visits, I would make sure you're wearing a good KN95. Go on Amazon, buy them, they're cheap. Or an N95 mask, which are obviously much more expensive. Okay, once you've done that, you know, if you wanna go to the grocery store, fine. If you wanna go to an indoor concert, probably not the best idea, right? Those are things that you're asking for it. I mean, we have the ASCO Conference coming up in Chicago, it was a big conference. You know, I agreed to speak to this and I was looking forward to it. I'm gonna be curbing the amount of time that I go to that, right? So those are things. Trips, okay, trips is another big one. You know, obviously the safest thing to do, if you can, is to drive somewhere. But people wanna fly and, you know, if you've been on an airplane and I've talked to a lot of people who have, 10% of people are wearing masks right now. And you can tell me until you're blue in the face how good the filtration is, but it's never gonna be good enough for you. And, you know, the truth is, I'm not saying don't fly, but again, you gotta wear a mask the whole time. And that's just something that you're gonna have to do. Cruises is another one Audrey brought up. I'm gonna inject a little bit of my own personal opinion, which is I would never go on a cruise before COVID. So that's my jaded opinion, but, you know, I've had people say, no, no, no, no, this is not like that kind of cruise. This is only 200 people and they're testing everybody and this and that. You know, I can't be the arbiter of what you, you know, you can and can't do. I think, you know, what you have to do is again, make sure that you can do everything in your power to protect yourself. So if you've gotten all of your boosters, if you've gotten, have you shelled, if you have antibody levels that, you know, at least are reasonably, you know, high, then I think you've done what you can to protect yourself against COVID. And you try to wear a mask is when you can in as many situations as possible. Eating is always a hard one. You know, I was invited to a friend's house or a family and friends, or it was Christmas and, you know, whatever it is. Those are hard, right? Because you're not gonna go and quiz everybody and say, show me your vaccine card. You can't, right? So there's just some risks that you do have to take. So I think limiting, you know, the number of people indoors is always helpful. But again, you know, you could get something that's not COVID, right? Human metanumavirus was affecting people a lot more this past few months than COVID was since the initial Omicron search. So I've rambled. I hope this is helpful, but the takeaways for me are, make sure that you have, you know, KN95 or N95 masks for indoor settings. When you're outdoors, go and live your life. Don't worry about that. But as far as trips are concerned, I'm not saying don't do it, but you have to accept the risk that this is possible. And also you have to have a plan in place, you know? I had a patient call me from, you know, they were on vacation and I said, I was a little early post-transplant and I said, I don't think it's the best idea, but they went anyway and, you know, they got COVID and they called me and I called in Paxlovid to their local pharmacy and they got it. And, you know, those are things, but you have to be ready to jump into action for those things if you're going to. Yeah, that was a great answer. Thank you for going into depth on that because I know that it's a constant worry that's on the mind of the myeloma population and our myeloma community, so thank you. Let's try to just go one by one with these questions that are left. Sure. There's really great questions. So someone's asking, you know, what blood, what lab is it that I should be looking at to see what disease-fighting cells that I have? Well, the easiest one is to look at, you know, the total white blood cell count and then of course the neutrophils, the absolute neutrophil count. So what you're looking for is a number greater than one. Your doctor will be looking at that too because oftentimes they won't continue treatment if you're below one or 1,000, depending on how you say it. But that's a, you know, a key number that we look at on a day-to-day basis. You know, after transplant, all the lymphocytes are down, but the key lymphocyte subset that we look at is something called CD4 cells. They're a type of T cell. And that's not routinely monitored, you know, on an everyday basis, but actually at the two-year mark, we vaccinate everyone for measles, mumps, rubella, and it's a live virus. And you don't want to give a live virus to somebody who has low CD4 counts because they might actually get infected. So I will check a CD4 count before I give the MMR vaccine. And as long as it's greater than 200, I usually in good shape. The same principle can be applied for back-term prophylaxis. I mean, a PCP prophylaxis where, which will answer Gretchen Collingwood's question, you know, the PCP prophylaxis story is probably most relevant for people who have a CD4 count less than 200. We know this because of data from the HIV patients where we've been using back-term prophylaxis for a long time for people with a CD4 count less than 200. Now, I'm not going to suggest that my alone patients have the same level of immunosuppression as an uncontrolled HIV patient. That's not the case. Everybody has kind of their own voodoo around PCP prophylaxis. But if you want to know the numbers, they actually have done the studies. It's probably somewhere less than a half percent risk of PCP after transplant, okay? What's PCP? PCP is the Pneumocystis Gervicii Pneumonia, or PJP, PCP. Okay. This is the one that we use back-term to prevent. So the risk is about 0.4%. You know, so, and it was actually regard, it really wasn't different whether you took prophylaxis or not. So, you know, whether you're on SelenX or after CAR T on anything, I really don't feel strongly about it. And I used to do it all the time. It's just over time, it gets cumbersome, you know, taking it three times a week or twice a week is hard to remember. It's actually harder than remembering to take something every day. So I typically don't recommend it. You know, I don't know of any evidence Gretchen about, you know, patients on SelenX or causing that. Again, it's not to say what anyone's recommending to you is wrong, it's just that everybody deals with uncertainty in a different way. And in fact, SelenX or, I mean, you know, we're not really seeing an increased incidence of infections. It definitely lowers blood counts, but I haven't anecdotally, I haven't seen in the literature any evidence, increased evidence of infections. The only one that really does is Venetoclax, which is not actually approved for myeloma, but it can be used in myeloma, of course. And actually there was a higher risk of fungal infections in those patients. So for that, in that case, I usually do start with antifungal agent. The weird quirk there is that there's an interaction between those two meds. So fluconazole, for instance, which is the most common antifungal that we use, actually doubles the efficacy of your Venetoclax. You might think, ooh, that sounds great, but it actually increases your side effects too. So you've got to drop the dose of Venetoclax in half if you're using both together. So I will usually start levofloxacin and fluconazole in Venetoclax patients, at least to start with. Venetoclax is commonly used for 11, 14 patients, right? Exactly. Cool. That's where I would use it, yes. Right, yeah. Okay, Ron is wondering if acyclovir is needed if you're on an IMID and a deratumumab, but not on a PI. You talked about how PI increases the risk. What if that's not part of your treatment regimen? I would still stay on the acyclovir only because it really has no side effects. I mean, I would challenge anyone on here to tell me that they've had a side effect attributed to acyclovir. I have it in every single one of my patients, I have hundreds of patients on acyclovir. It's annoying, the pill is big, I get it, but it's cheap, has virtually no side effects and why risk it? I don't know that there's any data with deratumumab, but the problem is everything is often combined with a PI or an IMID, so it's really hard to know, but at least for IMIDs, it does not appear that that is in itself associated, but for all my patients on maintenance therapy with lenalidomide, for instance, I still have them on acyclovir. We do have a study right now where we're actually discontinuing maintenance therapy for patients who are MRD negative. It's beyond the scope of our talk today, but in those patients, I do eventually stop acyclovir and that's a situation where I say, yeah, sure, why don't you get the shingles vaccine? Because then you'll just stop acyclovir and you'll at least have some protection against shingles moving forward. You don't wanna get shingles, that sucks. Yeah, yeah. There was actually a question related to that that I'd like to jump to. Said, given your immune system would be further reduced if an MMPatient achieves MRD negativity, which I believe lots of the population here today and our audience understands, would you still recommend getting a stem cell transplant? Okay, so let me just unpack that. I think where the question is, a good one, which is, let's say you get to MRD negativity. There's no detectable disease, even in the most teeny tiny amounts that we can look at, millions of cells that we look at. Should you still undergo a stem cell transplant knowing the side effects, the toxicity and the immunosuppression longer term that it can cause? This is very controversial. I would say even if you take the immunosuppression out of it, this is a controversial question. Right now, what I'm counseling patients is not to go based on a single MRD result after four to six cycles of treatment to make a determination about transplant. Because what you're really interested in is, what's it gonna look like in a year from now? If I continue the treatment that I'm on as is, am I gonna still be MRD negative? Because you really need to have sustained MRD negativity to really get that long-term benefit. And there's no guarantee that transplant will make that any better. It does seem to be the case from some studies so far. The transplant related mortality, meaning deaths that can be attributed to transplant, infections, et cetera. It's exceedingly low in myeloma. It's basically 1% or less. Which means that you can feel pretty confident that when you're going through a transplant, these things can be mitigated. In fact, my post-transplant patients who are on Revlimid, I've noticed a very peculiar phenomenon, which is those are not the patients who are not having antibody responses to the COVID vaccine. Like all of them have very high antibody levels. I haven't had to give many of them Abuchel because I've found that their antibody levels are very high. Which tells me that the immune system has actually over time not only been reconstituted, but seems to be at a level that is adequate, right? Along those lines, I'm gonna answer Jade's question about revaccinations that can be skipped. I wouldn't veer from the schedule, especially with polio and these things. I think what you're arguing is there's no polio. Why do I need it? But I'm gonna point you to the monkeypox cases that we have right now as an example. In Utah, we're in Miami. You don't wanna mess with this stuff. I mean, these are vaccines that literally saved us from horrible, horrible illnesses. And God forbid something happens down the line, you wanna make sure that you are protected. So I do still incorporate polio vaccinations into our, and that's actually a CDC recommendation as well. Well, Dr. Duran, let me ask- That's put her bad these days to be endorsing everything the CDC says, but anyway. Let me ask you a follow-up question with that because a lot of patient frustration comes from varying vaccination protocols and rescheduling in transplant centers. So how can a patient adequately educate themselves about what vaccines are needed because it differentiates all over the nation? Yeah, this is something that I actually, when I started, I said, why is this the schedule that we have when other people have a different one? Things change, right? I mean, of course we're gonna be vaccinating for COVID and have a strategy for that. I think what you have to think about are what are the most common things that could get me? And then what are the horrible things that of course we have vaccinations for that we would want. So, I mean, I'm interested in this because I see my children go to the pediatrician and I'm like, oh yeah, it's similar, right? I mean, we're doing a lot of the similar things. So the first thing that we do is focus on pneumonia shots, Pneumovax and Prevnar. Now there's actually Prevnar 15, but we haven't been incorporating that yet. We may eventually, but, so those not only decrease the chances of getting strep pneumoniae infections, predominantly pneumonias, but they also decrease the chances of having a severe infection, right? And I just told you how pneumonias are one of the most common things that get my alone patients. So, that's a key one that you wanna make sure that you're getting. And we actually revaccinate people with Prevnar several times to build up that immunity. And you can measure your antibody titers against the 23, what they're called serovars, which are basically the species of strep pneumo that we vaccinated against. And you can see if you have immunity against them. I mean, I don't know if it's worth doing, I just vaccinate anyway, but that's one thing. Starting around a year, we then do the baby shots as I call them, tetanus, diphtheria, pertussis. If any of you have grandchildren or children yourself, this is definitely one that you wanna get. I mean, our OB-GYN said, you can't have parents coming around unless they've gotten Tdap anyway, right? So, that's a no-brainer. Hepatitis B is another one that you wanna, it's a no-brainer. I remember when I started my residency, I actually didn't have hepatitis B titers, my immunity waned, and I had to get revaccinated for that. So, that's just a very common thing to wanna do anyway. Polio we talked about, and then hemophilus influenza B is not the flu shot, but is a different one. I also recommend the flu shot, but hemophilus influenza B is another important one against pneumonia, for a type of pneumonia. And then the last thing is measles, mumps, rubella. That's not going away, because not a lot of people are vaccinating their children now, depending on where you're at, probably more on the West Coast than everywhere else, but still, that's a major issue. Yeah, thank you for sharing that. One question that was asked was about the risk of being with young grandchildren. Will you briefly speak to that? They're little Petri dishes, take my word for it. That doesn't mean don't see them, but most of the infections I saw in the last four months that weren't COVID was, my grandchildren were over and we were playing and they were sniffling around and I wasn't wearing a mask. You know, this is the thing. I mean, it's just very, very common right now. So I know it's hard, you know, these are things that you, these are so important. You wanna spend time with your family, you wanna spend time with your grandchildren or your children. You know, from the grandchildren piece, I recommend, you know, making, you know, you gotta ask the parents, do they have any symptoms? If so, I wouldn't have them come over, you know? I mean, it's just not worth it in the long run. And if they don't, you know, I think it's not like you have to be wearing a mask every time, but certainly in the early days, post-transplant or CAR T, that might be something where you do wanna wear a mask, you know, for the first three to six months, if you're around them, you know, just cause you don't know exactly what they're doing. I see a lot of questions about, have you shelled? Yeah, let's tackle those, yeah. Okay, is it on board as a booster effective or does it neutralize the effect? Doesn't neutralize the effect of a booster. It's totally different. This is really ideally, so instead of you making the antibodies yourself from the vaccine, it's giving you the antibodies. It's just like, it's like getting the answers to the test, right, you just give you the antibodies. So it doesn't get negated by transplant because the chemo doesn't kill antibodies. It might kill plasma cells that make antibodies, which is why we wanna give it even before transplant. So it's really ideally used for people who are about to enter into or have already been in a situation where they're not going to be able to make antibodies. So for my patients who actually don't have like any detectable antibodies or very low levels, it's a perfect solution to me to try to mitigate that risk. So do I give, have you shelled if there's a positive antibody test? I would say most people are gonna argue, how do you know what, just because it's positive, how do you know what the levels should be? I've gotten, this is very unscientific, but I've gotten a sense of like what's a high level and what's a low level based on our antibody test here, right, so after the number of boosters that people have gotten and whatnot, for us, the antibody level should be sky high. And if it's not sky high, even if it's just like positive, but low level positive, I'm gonna consider those as the same as those who are undetectable. So I would use every shelled in those circumstances, but I have been forgoing it for people who have very high levels. Have you shelled can cause the M spike to increase slightly similar to like the way Daratumumab or Elatuzumab would, it'll be just faintly positive. So if that shows up after you've gotten an EBSHELD, that doesn't mean the disease is coming back necessarily. And I answered this, it doesn't, I mean, yes, it survives transplant. Because it's an ant, it's not, the chemo's not killing the antibody. It's not a living cell. Yeah, that makes sense. The protein, so it will wane over time, but that's separate. Yeah, do you have a couple more minutes to answer some questions? Yeah, yeah, yeah, I'm gonna try to, I'll just try to rapid fire to you. So how long should I be on a cyclavir? I think I've given you my opinion on this and I get no money from whoever makes a cyclavir. I would stay on it for as long as you can. It does not cause long-term organ damage. I have never seen that, never heard of that, never seen it. It's very safe, very safe to use. I mean, we give it all the time to people as on-demand therapy, if they get cold sores or whatever. Anyway, Dapzone. I do use Dapzone occasionally. If I was going to use Bactrim and for some reason, they could not use Bactrim because of a sulfa allergy most commonly. It's important to check something called a G6PD level before you start Dapzone. G6PD is a protein that's basically made and it can be, you can have a congenital deficiency in it where you don't make G6PD. And if you don't, your red blood cells are more likely to get split open if you're exposed to certain agents. Dapzone is one of them. So before giving Dapzone to anyone, you wanna check a G6PD level, but you certainly can use it. It's generally fairly well tolerated as well. It doesn't cause low platelets like Bactrim can. I get COVID, is it more likely to be a severe illness? The data suggests yes. Most of the COVID that I've seen in the last five, six months in our vaccinated patients haven't been severe, but it'll probably depends on other underlying things like obesity more commonly causes severe infections, underlying COPD or asthma, emphysema or asthma more likely to have things like that. If I'm in remission, then I have normal plasma cells being made. Why am I still immunocompromised? We don't really know this. This is a good question. You don't really know this. I mean, if there was a way to survey your whole entire immune system and give you a number or some way to say that your immune system has been reconstituted, that would be great. The first thing that's helpful is to see, certainly people who are off treatment are going to be closer to that immunocompetent status. If your immunoglobulin levels are normal, your white cells are normal, your neutrophils are normal, your lymphocyte levels are normal. Those are all good signs that you could be pretty close to the normal population. I would say in these day and age, maybe it's more in your mindset, but probably doesn't hurt to be labeled as immunocompromised because you get access to a lot of the therapies that ultimately are gonna be rolled out to everybody else, but you get it sooner. What else we got? And Burl is wondering, what's the risk of outdoor professional sporting events? All I answer, I'm just kidding. Just from my experience, that's where my mom got COVID was an outdoor football game and then spread it to literally everybody that she knew. So I don't know your opinion on that. I don't know, because the outdoor piece of it, like if you're at the park, right? Yeah. I mean, you're not really gonna be at high risk. It's not something that can really spread outdoors. Outdoor sporting events is an interesting one though, because it's people in really close proximity to each other, so it's a very large space, but you could have 40, 50,000 people in one area. And if you were just staying in your seat at the ballpark or whatever it is, okay, maybe it's fine, but you're not, right? You're going to the concourse and you're going into the bathroom and those are all indoor things, right? So it's really hard to guarantee that you can be completely outdoors that whole time. I'd still recommend people wearing a mask if they go. So that's- And it's so hard, because just again, back to the, we're not, we want patients to have a high quality of life and we don't want them to stay stuck or in fear in their house forever. It's a really, it's a really uncomfortable balance that we are figuring out. It is so true. I mean, anybody that does less than you is crazy. Anybody that does more than you is crazy. And your risk tolerance is on display for everybody all the time. It's exhausting. It's exhausting. I find it exhausting. And everybody's a hypocrite to some extent. They won't do this because it's not that important to them to do it. So they'll say no, because it's easy to not offend anyone and just say, because of COVID stuff. But if it's something you really want to do, right? You won't do it. You may not go to your second cousin's dance recital because like, who the hell cares? But you want to go on the cruise with 200 people, right? I mean, I don't mean to be flippant about it, but that's what's going on right now. Well, yeah, it's just the reality of today. Yeah. Okay, Judith is wondering, should we ignore all those who question the safety of the COVID vaccine? Oh, that's actually Steve, but same question. Okay, my short flippant answer is yes, ignore all of them. My long answer is, okay, we've had a billion people vaccinated against COVID at this point. I'm not here to convince anybody else to vaccinate themselves if they haven't already, because I kind of know that it's not worth the time and effort, but for those of you who still believe in the science that has led to this, don't doubt yourselves. It's absolutely perfectly safe. I will say this, having vaccinated people four or five times over, we haven't had to do that with every other vaccine, except for maybe flu. I think there is going to probably be a different vaccine that we will roll out at some point later down the line, but this is the best that we have right now, and it's saved a lot of lives. So I wouldn't doubt that. Yeah. Sky-high antibody numbers, it really depends on the assay and then the institution, I can't get into it. If it was an R assay, that looks actually pretty good to me, but this 850 number, but again, if someone's checking it, unfortunately they're stuck with having to interpret it for you. I don't want to be the one to interpret that for you, but this is why people argue don't send it because you don't know how to interpret it. So how many times can you get out of your shell? Well, like everything with COVID, we do it once and then we see what happens. You probably are going to need it repeatedly every three, four, five, six months probably. In general, IVIG for instance, we give every six weeks, which is an antibody infusion, but antibodies have a long half-life so they can stick around for a while. So it may be that you need to check antibody levels and then when they fall again, then you re-dose. My guess is it'll probably be every six months or something like that, which most people haven't gotten quite to that point yet. This last question is essentially asking about boosters. How many boosters are recommended? And kind of if we could go over one more time, what's the protocol for vaccines and boosters? Okay, so pretty much anyone with myeloma on this call or related disorders on this call, my recommendation is the following. I would do, if you have not done your initial series, I would do your initial series. Initially that was two shots, now it's three, but assume most people got two. Then you get two boosters, each one about three to four months apart from the initial series, if not longer. That's four shots total of maybe five if you've done the whole way the CDC recommends now. And then for those who are checking antibody titers, if they're low, I would do Abucheld. If you're on drugs like daratumumab or going into transplant or CAR T, I would also do Abucheld regardless of your titers. And that's just based on some of the evidence that we have. One does not negate the other. I usually don't do them on the same day. I don't give Abucheld and the vaccine on the same day, but yeah, I mean, I usually try to separate them out closer to like three to four weeks, but there's no science behind that. That's just my own approach to it. That's my COVID sort of, that's what I'm doing in the clinic right now. It's one person's opinion. Yeah, thank you. Well, thank you, Dr. Numan for this excellent presentation. This was exactly the kind of conversation I was looking for and I really appreciate the time you took in preparing for this, so thank you. Absolutely, thanks everyone for awesome questions. Yeah, yeah. My audience has always come through with extremely educated and excellent questions. It's a pleasure. Let's, I'll just close with a couple of outro announcements and then we'll be done for today. You can join us in July as we learn more about POMELIS, POMELITAMID, that's used in the relapsed refractory setting for myeloma patients. We're gonna be learning about its mechanism of action, side effect profile, its relationship with ReveLMID, and its efficacy and more details on this are to come as we get closer. You may be interested in other myeloma crowd events. Tomorrow is our African-American myeloma community chapter. We'll be talking about how to change your diet while keeping your culture. There are tomorrow as well, tomorrow evening, we have, oh, that's the evening, sorry. So that's gonna be at 7 p.m. Eastern is our newly diagnosed myeloma patients chapter. It's gonna be clinical trials for newly diagnosed myeloma patients, which is extremely important. Lots of people think clinical trials are just for the relapse refractory, but it's even more, well, not even more crucial, just as crucial that we get newly diagnosed patients in those clinical trials as well. And then on the second, where it's gonna be our health training moves for myeloma chapter, we're gonna be talking about water aerobics and the benefits that that can have for myeloma patients. The link to sign up for those events and even more events I have not mentioned is found at the bottom of this slide and will be sent out in our follow-up email. As always, whoops, as always, I'd like to thank our sponsors. Without him, this would not be possible. Brista Meyers-Squibb, GSK, Genentech, Janssen Oncology, and Abbby. And a big thank you to each of you for helping us grow this myeloma community. It's a pleasure to be with you. And thank you again, Dr. Dermin, for your time. I hope that you have a great rest of your day, everyone. Oh, and one question, Dr. Dermin, to you. Are you willing to share your slides? Oh, sorry, you're muted. I'll send them to you. Yeah, perfect. And then I can distribute them. Yep, perfect. Okay, thank you so much. Bye-bye, everyone. See you, everybody.