Standardization of Outpatient Care after CAR-T Therapy across a Large Cell Therapy Network- through Technology and Decentralized Virtual Nurses: Preliminary Results
Authors: Cox Tonya , Zahradka Nicole , Billups Rocky L. , Blunk Betsy , Campo Rebecca , Carelock Trista , Husband Mary , LeMaistre Charles F. , Majhail Navneet , Martin Casey , Meissner Sarah , Pantin Jeremy , Perez Meredith , Pugmire Juliana , Ramakrishnan Aravind , Shaughnessy Paul , Smith Ashleigh , Tees Michael T. , Wilkes Matt , Yates Megan , Battiwalla Minoo 
Published: December 2023

Introduction: Shifting Chimeric Antigen Receptor T-cell (CAR-T) therapy to the outpatient setting may increase patient satisfaction and inpatient capacity, and reduce infection risk. Outpatient protocols require resources for patient management outside of clinic hours to be safe and effective. Our Transplant and Cellular Therapy Network (TCTN) leveraged wearable technology and decentralized nurses in four outpatient CAR-T programs. We sought to characterize patient adherence, time spent on patient monitoring, and clinical outcomes.

Methods: Patients were deemed eligible for outpatient therapy if they were adults (18+ years), lived within 30-60 minutes of the treating hospital, had a 24/7 caregiver, and received CAR-T with known risks of developing cytokine release syndrome (CRS). The outpatient CAR-T program included enrollment into an FDA-cleared virtual care platform, daily engagement with virtual nurses for the duration of the program, and in-person clinic visits during the highest risk period (Days 1-14). The remote monitoring kit included a wearable device that continuously transmitted vital signs (pulse, respiratory rate, O 2 saturation and skin temperature), a tablet, axillary temperature patch and blood pressure (BP) cuff. Patients were asked to always wear the device outside of clinic visits, take a BP reading 3x/day, and complete surveys via the tablet. A multidisciplinary taskforce established clinical pathways for remote monitoring across sites and developed parameters for alarms, virtual nurse check-ins, and escalation of care to ER/clinic. Virtual nurses contacted patients based on vital sign trends, responded to patient concerns, and triaged in accordance with clinical pathways, escalating as appropriate.

The virtual care platform, video and phone call logs with the virtual nurses, and clinical data were extracted for 40 patients between 2/20/23 and 6/15/2023. Inpatient admission, patient adherence, alarms, calls, and clinical metrics were summarized. Non-parametric measures were reported as median (IQR). Metrics for specific windows of time were reported for a subset of variables: wearable adherence (day vs. night) and alarms/calls during clinic hours (weekdays 8 am - 5 pm) vs. non- clinic hours. Adherence was derived from tasks/wear time completed vs. prescribed.

Results: Forty patients (66 ± 12 years, 24 male) with diagnoses of Non-Hodgkin Lymphoma (75%), Plasma Cell Disorder (20%), or Acute Lymphoblastic Leukemia (5%) received CAR-T therapy [axi-cel (40%), liso-cel (25%), cilta-cel (20%), brexu-cel (12.5%), tisa-cel (2.5%)] and completed the outpatient CAR-T program. The median length of monitoring on the platform was 14.7 (10.4 - 27.6) days. Overall wearable adherence was 79 (67.7 - 87.9) %; 67 (48.7 - 83.4) % in the day and 89.1 (79.8 - 92.8) % at night. Median survey completion was 50 (7.7 - 80) % and BP compliance was 95 (69.8-100) %. Out of 717 patient days, 68.4% had 100% BP compliance (3 readings/day). There was a total of 780 alarms; 67% operational and 86% clinical alarms occurred during non-clinic hours (Table 1). The operational alarm rate was 0.5 and the clinical alarm rate was 0.6 per patient-day. 75% of patients triggered at least one operational and clinical alarm during their program. The virtual nurses engaged in 1102 calls through the tablet or phone (3.5 ± 3.4 mins). More than half of the calls were during non-clinic hours (63%) and 70% of calls were with a patient/care giver. Calls about a clinical alarm or clinical concern were 3x and 6.8x higher, respectively, during non-clinic hours.

Twenty-seven patients required some level of hospital observation service and/or admission to the hospital; 25 patients developed CRS. Median duration from infusion to admission/observation was 5 (1-11) days. Median days to discharge was 5 (1-26). Of those admitted,10 patients were admitted to the ICU with a median stay of 5.5 (1-21) days.

Conclusion: Our TCTN established a successful, integrated outpatient management process to ensure patient safety within the first 30 days post CAR T-Cell therapy. The virtual care platform and decentralized virtual nurses have enabled patients to recover safely with more time at home rather than in hospital. Future research will address patient and provider experiences and continue to expand on the safety and resource utilization of this integrated program.