Comparison of 15- Vs. 30-Day Remote Patient Monitoring for Outpatient Chimeric Antigen Receptor T-Cell Therapy (CAR-T) across a Large Health System
Authors: Cox Tonya , Zahradka Nicole , Martin Casey , Blunk Betsy , Billups Rocky L. , Meissner Sarah , Sowell Hannah , Larson Stephanie , Perez Meredith , Ramakrishnan Aravind , Shaughnessy Paul , Smith Ashleigh , Tees Michael T. , Pantin Jeremy , Zaniello Benjamin , Majhail Navneet , Battiwalla Minoo 
Published: December 2024

Introduction: Remote patient monitoring (RPM) is a critical component of successful outpatient (OP) CAR-T, greatly reducing time in the hospital. The OP monitoring period following CAR-T is roughly four weeks to enable early intervention for toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The optimal duration for RPM within the 30-day monitoring period is undefined. Previous work has shown that the incidence of new onset CRS and ICANS is low beyond the first two weeks post-infusion. Our primary objective was to compare clinical outcomes and the secondary objective to evaluate adherence metrics for 15-day versus 30-day remote pt monitoring across four Sarah Cannon Transplant and Cellular Therapy Network (SCTCTN) sites.

Methods: Adults (18+ years) living &lt;60 minutes from the treating hospital, with a 24/7 caregiver, who received non-investigational CAR-T and met OP criteria were eligible for OP administration. RPM involved enrollment into an FDA-cleared virtual care platform, virtual nurse engagement, and in-person clinic visits during the highest risk period (Days 0-14). While the overall OP duration was 30 days, initial RPM was planned for first 15 days at one site and for the full 30 days at three other sites. The RPM kit included wearable devices that continuously transmitted vital signs (pulse, respiratory rate, and O2 saturation), an axillary temperature patch, a tablet, and a blood pressure cuff. A multidisciplinary taskforce developed clinical pathways for remote monitoring, including parameters for alarms, virtual nurse check-ins, and escalation of care to the designated emergency department (ED) or clinic. Virtual nurses monitored vital sign trends, responded to patient concerns, and triaged according to clinical pathways, escalating as necessary.

Data from 209 patients between 2/20/23 and 6/15/2024 were analyzed. 56% had NHL, 34% myeloma, and 10% ALL. Metrics were summarized by pgm duration (15 vs. 30 days). Clinical outcomes and length of stay (LOS) were classified as occurring in the first 15 days (Day 0 - 14), or between day 15 and day 30 (Day 15 - 30). Non-parametric measures were reported as medians (IQR). Adherence was calculated based on wear time completed versus prescribed. Wilcoxon matched-pairs signed rank test was used to compare patient adherence metrics between Day 0-14 and Day 15 - 30 in 30-day pgm.

Results: There were 97 patients [median age 64 (IQR, 55-72) years, 68% male] on the 15-day, and 112 patients [median age 64 (IQR, 55-70) years, 52% male] on the 30-day RPM pgm. There was a significant difference (P&lt;0.001) between CART products: Axi-cel (40%) being most frequently used in the 15-day pgm vs. Liso-cel (38%) in the 30-day pgm. The median monitoring duration was 10.5 (IQR, 7.7-13.0) days in the 15-day pgm and 25.8 (IQR, 21.1-29.6) days in the 30-day pgm. In the 15-day pgm, 25.8% of patients were extended by at least 2 days based on clinical judgment [median 3.4 (IQR, 2.7-5.0) days longer].

In the 15-day pgm, 86% of patients were hospitalized during Day 0 - 14 [median LOS = 4 (IQR, 3 - 8) days] and 14% of patients were hospitalized between Day 15 - 30 [median LOS = 3 (IQR, 2 - 6) days]. In the 30-day pgm, 82% of patients were hospitalized during Day 0 - 14 [median LOS = 6 (IQR, 3 - 9) days] and 9.8% of patients were hospitalized between Day 15 - 30 [median LOS = 3 (IQR, 2 - 5) days]. 98% of patients who developed CRS had onset occur in the first 15 days regardless of pgm duration. The onset of ICANS occurred approximately 2 days after CRS but still during the first 15 days in approximately 96% of instances. In both cohorts, no patient experienced grade 3/4 CRS beyond day 15 and only a single patient had grade 3 ICANS. 30-day overall survival was 97% and 98% in the two cohorts, respectively.

Overall patient adherence to wearables in the 15-day pgm was a median of 76.3 (IQR, 65.3-79.9)% vs. a median of 83.8 (IQR, 78.39 - 90.9)% in the 30-day pgm. There was no significant difference in adherence between Day 0-14 vs Day 15 - 30 in patients enrolled on the 30-day pgm.

Conclusion: OP administration using RPM and a clinical pathway driven program is safe and routinely possible with high rates of patient adherence. For patients receiving currently FDA approved CAR-T products, RPM monitoring for the first 15 days will capture the vast majority of CRS and ICANS.