Okay. Thank you for inviting me to give this talk. So I will be giving you an update on the cost and ICU utilization for cellular therapy. Wait. Which one are we using? Oh. Sorry about that. These are my disclosures. And we're going to be reviewing the current literature and cost of ICU utilization of cell therapy and mainly some of the FDA approved products. We'll recognize some of the main drivers of costs and we'll review some recent data on ICU utilization and interventions that might actually shift some of our practices. So I think since the beginning of CAR T cell therapy, we've all been very excited about the outcomes of a lot of these patients with B cell malignancies that had refractory disease. And a lot of these products are already being approved and we know this is the future. However, one of the questions that has been in the back of everybody's mind is what is the cost of this treatment? Who's going to pay for this and who's going to be able to afford the treatment? Now when you look at some of the data of the cost of this therapy, it's all over the place. And what I mean by that is everybody's trying to understand this a little bit better. They've looked at smaller studies, centers, national studies. And I think overall, you know, all of them think that this is a potentially cost effective alternative to our current standard of care, meaning chemotherapy. And it all has to do with the fact that these patients have increased survival and better quality of life. Now this all just depends whether or not if your patient is going to be able to survive in the long term. Now where do these costs come from? And I think when we were first starting to treat our patients, our biggest concern was just how expensive the cells alone were. We were also extremely concerned about the cost of IL-6 therapy. We were also very concerned about anakinra. And I think as we treat more and more patients and more of these studies come out, what we're realizing is that the biggest costs are actually occurring not when the patient gets treated, but once your patients develop toxicity. And mainly, once your patients start developing severe toxicities, grade three and more. If your patient has combined CRS and ICANN's grade three, just your costs are extremely, extremely high. Now what is striking when you see this, and this is sort of the dark blue line here, is that the majority of these costs are actually facility costs. So these are patients that will be in the hospital for a prolonged period of time. All of these patients will need ICU admission. And this is really what is driving the cost of this therapy. Now since the beginning, we sort of wanted to understand a little bit more about how these patients sort of compare to the general lymphoma population that is not receiving CAR-T cell therapy. We published a small study within our institution comparing CAR-T patients to lymphoma patients that were not receiving CAR-T cell therapy. And there's also some data, multi-center trial on pediatric population, also looking at CAR-T patients versus non-CAR-T patients that have been admitted to the ICU. And what is exciting, I guess, yeah, about this is, yes, a lot of these patients do get admitted to the unit, more than the non-CAR-T patients. However, this patient population, they actually use less high flow, BiPAP, mechanical ventilation, vasopressors, CRT, than any of the other patients. Also, there's probably less procedures in this patient population than the other patients. ICU length of stay is actually fairly similar between these two groups. And what is really exciting is to know that this patient population has a very low mortality. So this initial data was what told us, you know, we have to really be aggressive about supporting these patients, independent of what we might think might be extremely expensive. Now, when you look a little bit more about what really happens to patients in the ICU once they get admitted and they have severe toxicities, it's fairly limited. We probably have three larger trials, one which is part of the U.S. Lymphoma CAR-T Consortium, the CAR-T study, which is data from Europe, and our multi-center study here within the U.S. All of these studies show that, yes, about 27 to 35% of these patients end up admitted to the unit. Very few of these get admitted for other reasons that are not CRS or ICANs, about 5% or even less depending on the study. Many of these with CRS, but the vast majority of patients are actually getting admitted with ICANs to the ICU. Now, as I told you before, only 20% of patients will be requiring any organ support. And yes, status epilepticus, seizures, cerebral edema are present, but not as much as we actually thought they did. And the majority of patients, more than 50%, were just admitting for monitoring of their mental status without necessarily any aggressive interventions. We just want to watch them and make sure that if they deteriorate, we act promptly or just until they respond to therapy. So has anything changed since we actually published some of this data that could impact ICU admission and costs? So there's new products available, which suggest that have less toxicity. We're recognizing other toxicities that could lead to ICU admission of these patients, and there's optimization of treatment of these toxicities that we'll discuss a little bit more. So this is preliminary data that we have of our institution. You'll have to ignore a little bit during the COVID pandemic. But otherwise, what we have observed throughout the years is that even though we're treating more patients within our institutions, and this only is actually FDA-approved products. It doesn't include any of the other trials. What we've observed is that throughout the years, every year we admit less patients to the unit. So we're being able to keep a good amount of patients on the floors. And when we admit these patients to the ICU, the grand majority of these patients have grade three toxicities, and as I said before, mainly ICANNs. Now with these new products, as you can see here, all of these have been approved for B cell malignancies. And what you can see and what I want you to focus on is that as more products come out, we're seeing less incidence of grade three toxicities, either CRS or ICANNs. However, we're starting to realize that it's not only CRS and ICANNs what we're really seeing in the ICU. You know, we're starting to recognize a little bit more CAR T-related HLH, which is going to be very important for us as intensivists. Post-CAR T, cytopenias. They're becoming more common. They're very refractory, difficult to treat in these patients. And all of this just puts them at a very high risk of infections, and therefore probably being admitted to the ICU. And again, we still see a good amount of patients that get admitted to the unit with a multi-organ failure in the setting of disease progression. Now with these new products, does it mean that we're going to be having more patients but less toxicity? And we're still not there yet. I think that's sort of what everybody's sort of hoping for. It would be ideal that we could just sort of pick and choose exactly what product we would want. We're almost there, but not there yet. So you know, the manufacturing is not there yet. Also if you have a patient with aggressive lymphoma, for example, you might not have the time to actually just sort of pick and choose, and you're just going to have to treat the patient with whatever product is available. Now the other thing that I wanted to sort of talk about is whether or not comorbidities are having any effect on how our patients are doing, and whether or not if they're getting admitted to the unit. We used to be very cautious and worried about treating patients with comorbidities, and I think what we're realizing is that we're treating sicker patients. So in this study by Nastobil in 2020, looking at all the patients within the U.S. consortium, 40% of those patients were so sick that they wouldn't have met criteria for the initial SUMA trial, which is a huge percentage of patients when you think about it. However, grade three or more toxicities, either CRSI and ICANS, the incidence was exactly the same. The patient's length of stay was also very similar. ICU stay admission, exactly the same. And not only that, but the patient's response to therapy was exactly the same as the SUMA trial. So all of this is important for us as intensivists to know that even those sick patients, they might actually do okay if we support them appropriately. So are any of these things influencing what we're seeing in the ICU? And in our institution, we are. We're actually observing that every year our patients are older. They have more comorbidities. And we continue to admit mostly just patients with grade three toxicities. Our SOFA scores are pretty much the same. They continue to have sort of the same degree of organ support. And we are observing that maybe there's a trend towards a shorter length of stay in the ICU, decrease in ICU readmissions. And the question is if there's something they're doing on the floors treating these patients appropriately or even us in the ICU. Maybe we're doing a great job and that's why these patients are not coming back. So one of the things that we're doing is we're optimizing the treatment of toxicities. We now have guidelines for everybody to sort of follow. And I think that's made a big difference. We now have an akinra that we know that is mitigating the severity of ICANs. We also know that it's useful in the treatment of HLH. We also know that the early use of tocilizumab is good to avoid patients progressing into worsening CRS. And the same as the use of early corticosteroids. We used to wait very long before we used corticosteroids. Now we use them earlier, smaller doses. And I think there's a lower incidence of these patients progressing and ending up in the unit. Some future interventions that could impact the cost of these treatments. Starting to treat a lot of these patients in the outpatient setting. So we reduce the length of stay of these patients and maybe just sort of admitting them if they end up developing CAR T toxicities. We're also starting to treat patients earlier. So we used to treat these patients that had failed four lines of therapy. Really bad disease burden. Very bad protoplasm to begin with. And usually those patients end up developing really bad toxicities. So maybe as we treat these patients early, even with axicab that is known to be one of the products with higher toxicities, maybe these patients will start doing better and less of them will end up in the ICU. And we have some prediction models. They still need to be validated, I guess, at bedside. But trying to sort of figure out which are the patients that are at higher risk of worsening CRS, ICANs, or even developing cytopenias in the long term. So in conclusion, you know, severe toxicities and ICU admission are still the main drivers of cost when patients are treated with CAR T cell therapy. ICU admission is now mainly for those patients who develop severe toxicities. And we're starting to do a little bit less sort of those soft admissions for just grade one, grade two toxicities, or even just for monitoring. And I think as products, patients, treatment guidelines continue to be optimized, it's possible that ICU admission could decrease in the acute post-infusion setting. But I think it's important from now on and for all of us to start sort of looking into investigating is what happens in the long term. You know, not really regarding CRS and ICANs, but down the line, how do these patients do once they get admitted into the unit? That's it.

cellular therapy

CAR T-cell therapy

cost

ICU utilization

hospital stays