Wearable Tech for Early Detection of CRS in CAR T-cell Therapy | Sridevi Rajeeve, MD | IMS 2023

Hi, my name is Sridevi Rajiv. I'm an assistant attending at the Memorial Sloan-Kettering Cancer Center specializing in multiple myeloma and cellular therapies. Today, I'm here to discuss a poster we presented at the International Myeloma Society Conference in Athens, Greece, regarding an investigative trial looking at wearable technology for monitoring cytokine release syndrome in patients receiving CAR T-cell therapy. Now, why did we do this whole project, right? In the present format, CAR T-cells, or chimeric antigen receptor T-cell therapy, which is a form of novel immunotherapy, is given primarily in the inpatient setting. Patients come, get admitted to the hospital, and they stay for anywhere between 7 to 14 days, depending on the cellular therapy product. And we give the infusion on what we call day zero, and we monitor them for two weeks for any serious adverse effects like cytokine release syndrome. Henceforth, I'll be calling that a CRS, or neurotoxicity. Now, for these 14 days that patients spend in the hospital, they probably will experience cytokine release syndrome on maybe one to two days. So that's a lot of somewhere close to 10 to 11 days that they're spending in the hospital just being monitored. So our goal was to try to see in future, can we take these patients or a subset of these patients safely to the outpatient setting, because doing that will primarily decrease the burden on patients and their caregivers. Being out of the hospital will reduce your infection risk. Being out of the hospital may also help increasing access of these very efficacious therapies to smaller centers if they can do it in a non-hospital setting. And also, it may help us in increasing slots for patients, because you're not dependent on hospital beds to allocate slots for each patient. So with all this in mind, we wanted to see how can we safely take CAR-Ts to the outpatient setting. So we used a very safe and reliable method to monitor for these adverse effects. And that's where wearable technologies we believe can help in monitoring for cytokine release syndrome. So we designed an Investigate Initiator trial in which we were looking at wider signs captured by a wearable device that the patient wears for the duration of their stay in the hospital. And we compared them to wider signs that were captured as standard of care by nursing. And we found really interesting results, something that we were not quite expecting. What we set out to see was that were wearable devices feasible enough for patients to wear, and is it capturing data accurately? What we found was the following. So we approached 24 patients who were getting CAR-T at the Mount Sinai Hospital in New York City. That's where I did my hematology oncology fellowship training. And that's the time when this project was conducted. We approached 24 patients regarding this project. 22 patients were really interested and they enrolled. So that's a high uptake of 91%, which really in my mind, it's a kind of surrogate to how much interest there is in this technology and increased acceptance of patients. Out of these 22 patients who enrolled and stayed in the hospital and wore their device for 14 days, except five patients who did not show any signs and symptoms of clinical CRS, all the other patients had cytokine release syndrome and the vast majority of them were grade one CRS. What we found was that the device captured cytokine release syndrome in 100% of patients who did have cytokine release syndrome and that there were no missed events. We also then, at the end of the monitoring period, tried to analyze what was the time to CRS that the device captured and we compared it to when the nurses first recorded CRS. So we did that in two means. One, we tried to see when is the device picking up a temperature of more than 38 degrees Celsius, which is the clinical definition of fever. We called that a fixed threshold. We also tried to look at when the fever curve of a patient starts increasing and more than two standard deviations above a person's individualized baseline and we called that an individualized threshold. So by comparing these two methods, we saw that the wearable device was picking up fever earlier by both methods. With the fixed threshold method, we found that the device picked up fever at 38 degrees 46 minutes earlier than nurses first recorded fever and by the individualized threshold method we found that the device recorded fever a whole of 206 minutes before nurses even first recorded the first fever. And this is important. This big of a lead time or an earlier detection was not what we were expecting and it's quite surprising and it's a pleasant surprise because that lead time, if it is, once we finish the study and if found consistent, can be really useful when we take patients to the outpatient setting because that's the time we can call patients, do a clinical triage and if they are staying outside the hospital, can have them come back to the hospital, give them an early intervention so that their cytokine release syndrome does not progress beyond grade one to higher grades. So you are thereby acting early, you're detecting early, you're able to act early, prevent severe complications all because you're able to have a better means of detection by continuous viral science monitoring. I think this could very possibly represent the future of how cellular therapies and bispecific antibodies could potentially be moved to the outpatient setting with careful monitoring with a very reliable means of checking for adverse effects and if we are able to successfully move at least a subset of patients to the outpatient setting, that would be a big bone for patients because of improved access and improved patient experience with these therapies instead of staying 14 days in the hospital. So we hope to complete out the study very shortly in the coming weeks. We are already at 90% accrual and once we finish the studies, we are excited to present it in the form of a full publication very soon and share it with patients. Thank you.