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My name is Doctor Joshua Richter. I'm an associate professor of medicine at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, and a director of myeloma at the Blobotnik Family Chelsea Medical Center at Mount Sinai. And today I'm gonna walk through a presentation on implementing outpatient and hybrid models for delivery of BCMA by specifics in the realm of multiple myeloma. So, we have begun to utilize bi-specific antibodies and a very routine practice in the world of myeloma, and initially the outlay of this plan was mostly in an inpatient basis. Now, the step up dosing that's given with bi-specific antibodies is done to minimize the risk of acute toxicities such as CRS or icons. But as we've grown more comfortable with the administration of these therapies and dealing with their toxicities, we've begun to move this mostly outpatient, and again, there doesn't have to be all or none or black and white. There are uh appropriate shades of gray, and we can find the Goldilocks zone oftentimes with something like a hybrid model that we go do part of the procedure as an outpatient and part as an inpatient. So, I really wanna walk through some of the nuts and bolts of how we can optimize the strategy, both for safety and efficacy, and minimize the time that patients spend in the hospital. So, when considering uh moving BCMA by specific treatment to the outpatient, you need to think about uh really a multidisciplinary and multifaceted team approach, considering not just your healthcare team. In both the acute, uh, chronic settings as well, but also considering what's gonna happen after hours on weekends and holidays, making sure you have appropriate safety measures in place in all the different settings, evaluate the patient's caregiver support, cause this may influence your ability to transition to a mostly outpatient setting, and then what about using some modern day technologies such as televisits uh to optimize patient care without having them interact with the medical system. Uh, too often. Now, at the moment, we're really gonna focus on the BCMA by specifics, of which at the time of this recording, there are 3 FDA approved by specificstelistumab, L-ranatimab, and linvaseltumab. Pictured here are the four FDA approved by specifics, noting that talquetumab is a GPRC5D targeted agent. Now, the reality is there are some subtle differences between these different therapies. So, focusing on the BCMA by specifics, we recognize that tlistumab and L-ranatimab are administered in a subcutaneous fashion, whereas at the current time, Liveseltumab is administered intravenously. The ramifications of this are that the median time to onset of CRS is significantly shorter with linvaseltumab, uh, whereas it's around 1 to 2 days for the median time to onset for CRS with telitumab and el ranatimab, it's around 10 to 11 hours, uh, with linvaseltimumab. Additionally, because linvaseltamab is administered as an intravenous infusion, uh, there is a risk of infusion related. Uh, adverse events that can occur during the 1st 1 to 4 hours of initiation of the administration. Now, one of the things to really think about when implementing an outpatient or hybrid model for your body specifics or where some of the failure points may arise, and I think it's important to think about this. Because you wanna strategize how to manage these failure points before they happen, prior to initiating a patient on therapy and discovering in real time in an acute toxicity setting where there are gaps in your system. So, uh, think of a number of, uh, dimensions about what the potential consequences are as a result of some of these failure points. For example, delayed recognition of fever or rigors, meaning if the patient develops these symptoms, who is going to be the first person to notice if the patient is not able to? Do they have a caregiver? Additionally, when this happens, especially In off hours, who's gonna get that first phone call? If it's going to be July 1st and it's a first day intern who may be wonderful and bright, but may not know about these toxicities, is that gonna lead to a loss of uh proper care or a delay in proper care? So off-hour communication breakdown is a key failure point. Additionally, what is your emergency unit, uh, what is their level of knowledge with these issues? Uh, have they never seen this before? They're simply going to administer antibiotics and not necessarily giving therapy to manage the CRS or Ion. So, really trying to think about some of these pain points and how we might overcome them. So one of the ways that we can think about this is really going through a list of potential eligibility criteria from the patient, the institution, and caregiver standpoint to evaluate the appropriateness and eligibility of giving outpatient or hybrid model by specific antibodies. First of all, uh, what is the status of your patient? Are they able to use a BP cuff? Are they able to take their temperature? Basically, are they able to monitor and report their own vitals at a baseline? Do they have any underlying cognitive issues that may impair their ability to appropriately Report a new onset adverse events. Do they have, uh, a caregiver at home? Uh, do they have reliable internet? Uh, are they able to communicate through phone or through portal if they need anything? And what's their overall performance status? Additionally, we can further break this down in a very granular way because we recognize that some patients are gonna simply require inpatient step up dosing. They may have uh other comorbidities, or they may have very high burden disease and may be at risk for higher grade CRS or icons. Additionally, they may have significant comorbidities, making the entire step up process more risky. To that end, I think this chart here represents a nice view of starting to tick off boxes of a step down format from fully inpatient. To which dynamics we can allow patients to receive in an outpatient or hybrid model and all the way down to fully outpatient and again, a lot of this relates to the bulk and extent of the disease which may influence CRS and icons as well as the overall status of the patient and really thinking about this from stem to stern, recognizing that when you're starting to plan this, there's an entire pathway that must be taken into account. And this workflow diagram really thinks about it, from the initial thought process and making sure you have the appropriate infrastructure set up, and that includes uh training across not just the hematology and oncology staff, but support staff as well, uh, telephone answering systems, and when moving on to the multidisciplinary team, including your emergency room facilities, your intensive care units, your neurology colleagues, so that they may better understand and be ready, prepared to deal with some of these adverse events. Making sure you have SOPs to deliver appropriate patient and caregiver information to optimize knowledge and minimize issues throughout the step-up dosing process. Making sure treatment and data authorization, uh, that you have authorization to give the supportive meds as well as the therapy itself. The supportive meds including things like tocilizumab or IVIG, evaluating premedications, how much steroids you wanna give them, are there any drug-drug interactions. And then monitoring throughout the step up dosing process. Now, one of the things that we've done at our institution is really try to move this mostly outpatient, if we can for the majority of our patients. And there's a number of ways that we optimize this, and this really comes along with really being front loaded in terms of our efforts to make the treatment itself fairly uh inconsequential. One of the big things is making sure that we prevent infections. And the way that you can achieve this in some of the most. Waves are making sure that patient has up to-date vaccinations, particularly for the respiratory infections like influenza, pneumonia, COVID, RSV. We recognize that BCMA by specific antibodies will mute our, uh, vaccine responses and therefore having these vaccinations in our system prior to initiation of BCMA by specifics is optimal. When initiating therapy, make sure we provide them HSV VZV prophylaxis, as well as PJP prophylaxis. Additionally, if they are at risk for reactivating hepatitis B, they need HPV prophylaxis. We do recommend primary prophylaxis with intravenous immunoglobulin. We typically start this on cycle 2 day 1, recognizing that the majority of myeloma will be IgG subtype, and as these patients will typically be progressing at the time of initiation of BCMA by specific, if they have high IgG levels to begin with, giving them IVIG may further compound this, putting them at risk for hyperviscosity syndrome. But one of the biggest things that we've done is employ the use of prophylactic tosillizumab to reduce the risk and onset of CRS. And really what this has allowed us to do is kind of evolve along the pathway from completely inpatient. To hybrid models for many to completely outpatient for many of our patients. Now that the use of prophylacticosillizumab has both not been shown to diminish the effect of the BCA by specifics, but from an approval standpoint is currently listed in the NCCN guidelines as a recommended option for all by specific administration. And in our utilization, this has been data from our own institution, the use of either hybrid model or outpatient with the prophylactic toillizumab has resulted in almost no patients having significant CRS or icons, and the few cases are really only grade one and