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Hi, my name is Ajay Noka. I'm a professor in the Department of Hematology and Oncology at the Emory University Windship Cancer Institute. I'm the director of the Myeloma Program and the associate director of clinical Research. And today, in this module, we'll be talking about preventing infection-related morbidity during the continuous BCMA therapy. Here are my conflicts of interest. So I will not be discussing any off-label drug usage, and here are my disclosures. I'll start with the patient's case. This is a 74-year-old female who has relocated to our practice from Orlando. She was initially diagnosed almost 13 years ago. This is the most optimal induction therapy to date. So she got the RVD induction, received for 4 cycles or 5 cycles, and then moved on to get a stem cell transplant as a consolidation sometime in September of 2013. So she remained on leidomide post-transplant. And around 2020s, so during the COVID, COVID pandemic, so she moved to Atlanta, and that's when we assumed her career. And at that point, we started looking at the MRD testing by next-generation sequencing. And unfortunately, this patient never was able to get to the deepest remission that we were looking for, a threshold of 10 minus 6 MRD negativity. So as we continue to monitor her over, over the years, she started to lose that MRD response initially, and now has an IMW definition of biochemical relapse, and clearly showing that her M protein is measurable beyond the 0.5 g per deciliter. So, she's daratumumab naive, and she was offered a combination of daratumab and tlistumab based on the majestic three results, and she was started in February of 2026. She tolerated the treatments well, received the full doses of telistab, received the full doses of daratumumab, and now she comes in for follow-up, and she got the first response within the first month. She's in a VGPR and now the questions go to, which of the following do you not recommend for this patient? IVIG supplementation for the duration of my therapy. To continue fluoroquinolones as antibacterial prophylaxis for the duration of birth-specific antibody therapy. Recommend usage of growth factors for patients with higher than grade 3 neutropenia, with infection or fever, and grade 4 neutropenia while patients are receiving the bi-specifics. Recommend that the patients be up to date with all vaccinations, including the COVID, including screening for HPV, HCV, HIV, as well as the seasonal vaccines prior to the initiation of bi-specific antibody therapy. Last but not the least, recommend prophylaxis for PGP, HSV, and VCV for all the patients while they receive the bi-specific antibody therapy. The second question is which of the following statements is true. So here, receiving growth factors is a contraindication for patients receiving bio-specific antibody therapies. Option number 2, receiving tosuluzumab for CRS prophylaxis or CRS treatment is a contraindication for patients receiving bio-specific antibody therapies. Receiving both growth factors and tosuluzumab are contraindications. So now, last but not the least, receiving both growth factors and doscilizumab are not contraindications for patients receiving bi-specific antibody therapies. The learning objectives of today's Presentation is to talk about mostly the infectious complications, and I'll also touch base on the efficacy that led to the approval of these drugs. By the end of the uh our module, you should be able to answer both of, both of those questions that we alluded to before and be right on target with the, with the data that is provided. So, let's jump on to what led to the approval of these agents. Techlistmab, based on the magistrate one trial, had a 63% overall response rate, and majority, there's a deeper responses. And similarly, ERatab, based on the magnetism 3 study, had a 61% overall response rate. Again, as you can see, these are deeper responses, Majority of these responses of VGPR are better. And Lynvasulumab, based on the link of one study, had a 71% overall response rates, and all these three are BCMA targeting therapies. So, I'll also touch base on the telcatumab, which is a GPRCFID biospecific antibody, even though it is not a part of today's discussion, I want you to see what exactly happens in terms of the, in terms of the efficacy and the infectious complications as a comparator compared to the BCMO bi-specific antibodies. So here, all these 3, all these 4 drugs were approved based on a single arm phase 2 studies. Of course, these are large studies, but these are based on single arm large uh single arm studies based on conditional approvals that eventually there would be a randomized phase 3 studies that would show the superiority of these agents compared to the standard of kit therapies, which will lead to a full approvals. And we've reached that case with techlist map, and I'll go through with, with, with that specifics in a second. So, let's talk about what the immediate complications would be. So, patients would receive, uh, would have cytokine release syndrome. Majority of these are, are grade 1s. So, grade 3 events happen extremely rarely. If you think about the 165 patients that enrolled in tech in that majestic 1 study that led to the approval of teclistab. Uh, there is one grade 3 event. Similarly, among the 289 patients that, that got, uh, that received telcatumab, there are 2 patients that received a grade 3 toxicity in in terms of CRS. So in the larger picture, CRS is not something that I'd be worried about today. So using docilizumab is not a contraindication, and these patients could be receiving docilizumab. It does not affect the efficacy, it does not affect the safety. So, please feel free to use dosuluzumab in, uh, to decrease this rate of CRS so that you can continue to give these therapies, and the patients could get benefited with that. So when that CRS happens, very early on, so at the 2-day mark, both with the teclizumab andanathimab, that's a median time. And when you look at the levosultumab, it happens at the 11 hour mark, the difference being, this is an IV formulation, and the CMax will be. Much, much higher with this formulation. So the reality is the CRS happens much quickly with the, with this limulab compared to the other agents where you expect to see with a subcutaneous formulation with telisab, Eatab, and teketmab, you expect to see the CRS happening at the 2-day mark. So in terms of the neurotoxicity, there's no higher grade toxicity in terms of the neurotoxicity. These are not like the car keys where you expect the Parkinsonism and the, and the delayed uh neurotoxicities. Majority of what we call as these do not even fit the criteria of ICAS. So headaches, likely, and peripheral neuropathy are the two things that we've seen across the board, but these are very, very manageable. So, with this, having said, uh, what the efficacy and the immediate toxicities look like, so the initial approval for is, for all these 4 agents is for relapse refractory multiple myeloma patients that have seen more than 4 prior lines of therapy, including an MIPI and a CD38 antibody. Let's talk about the, the crux of today's talk. So what happens with these BCMA uh targeting by specific antibodies, and I'll also provide a context in terms of what happens with the other modality BCMA targeting CAR T therapies. So let's talk about the Karma 1 and the Karma 3 studies that led to the approval of IAsil, and here it is approved for patients who had seen more than 4 prior lines of therapy, including a PI image and a CD38 antibody, but a confirmative trial with CARMA 3 compared to the standard of care therapies led to the approval of IDel among patients who had seen 2 prior lines of therapy, according to the FDA. So these patients should be len refractory, and if they've seen two prior lines of therapy, IDil is approved. So if you look at all these, so they're all grade toxicities are in terms of the infectious complications, you see that in 3 of the 5 patients that were treated. So 60% of the patients would have all grade infections related to Iosil. And when we talk about this grade 3 and grade 4 toxicities that you see in the second and the third columns, so these are higher grade toxicity, greater than grade 3, which means a patient needs to be hospitalized for an infectious complication. So that is happening in the range of around 20% to 25%. So the same thing goes on with Celtasol. Celtasil was approved based on the cartriitude one trial, and in the In the late relapse setting among patients who had seen 14 prior lines of therapy, including a PI immediate and a CD38 antibody. Cochin 4 is the one that led to the approval of Silsan as, as an early line of therapy among patients who had seen at least one prior line of therapy and who should be land refractory. And among these two, you see the exact same grade 3 and 4 complications accounting for around 25 to 30% of patients. So that number increases when you look at the majestic 1 trial, the magnetism 3 trial, and the Linar MM1 trial. All these 3 are BCMA targeting bi-specific antibodies, and the infection rates are almost like you treat 5 patients, 4 of them will have an infectious complication. So, there is.