Delivering CAR-T and bites outpatient: A safe and resource-conscious model for T-cell redirecting therapies

Abstract

Abstract Background: T-cell redirecting therapies (TCR), including CAR-T and bispecific T cell engagers (BITEs), have changed the treatment landscape and prognosis for patients with relapsed lymphoma and multiple myeloma. Due to the risk of CRS and ICANS, administration of these therapies requires close monitoring, which has traditionally been done inpatient, based on the registrational trials. Some patients experience no significant toxicities, resulting in non-therapeutic hospitalizations that strain healthcare resources. While several real-world studies demonstrated the feasibility of outpatient administration, implementation remains logistically challenging, requiring dedicated infrastructure, care coordination, and rapid response systems. A standardized approach is lacking. Here, we present our institutional model for outpatient administration of all BCMA- and CD19-directed CAR-T products and myeloma BiTEs. Aims: To evaluate safety, feasibility, and healthcare resource utilization with outpatient TCR program. Methods: Patients who received inpatient (IP) or outpatient (OP) CAR-T or OP BITE step-up dosing (SUD) were included in the retrospective analysis. Student's T-test was used to compare between groups. A pilot OP CAR-T program was launched in 11/2020 for selected patients based on the payor agreements. A universal OP CAR-T protocol was implemented in 11/2024. The OP BITE step-up dosing (SUD) program was implemented in 12/2022. Eligibility criteria for the OP TCR program include availability of a dedicated 24/7 h caregiver and ability to stay within 60 min distance from the center and undergo daily standardized toxicity assessment in the clinic throughout the product-specific monitoring window (housing is provided if needed). The BITEs SUD schedule was modified to be administered on days 1, 3 and 8 starting Monday, to avoid weekend monitoring. Patients and caregivers receive education on CRS/ ICANS, and are instructed to monitor vital signs and signs of neurotoxicity at home every 8 hours, and to contact the center immediately if any concerning symptoms occur. All patients are provided with wallet cards to streamline recognition of TCR-related toxicities by all providers. Affiliated Emergency Department staff also received targeted education on CRS/ ICANS and management protocols. Providers trained in cellular therapies are available 24/7. Patients are promptly admitted for management of any grade CRS/ ICANS. Results: 111 pts were treated in the OP program. Of 167 CAR-T pts treated at our institution, 104 received CAR-T IP and 63 OP. Products administered included ide-cel (20 IP, 9 OP), liso-cel (11 IP, 15 OP), cilta-cel (10 IP, 15 OP), axi-cel (51 IP, 9 OP), tisa-cel (4 IP, 11 OP), and brexu-cel (8 IP, 4 OP). The median age was 66 years in both groups. The median number of IP days in the first 30 days post CAR-T infusion was significantly lower in the OP group compared to the IP group for liso-cel (1d vs 6d, p .001), cilta-cel (3d vs 8.5d, p .003) and axi-cel (5d vs 10d, p .001). No difference was noted for brexu-cel, while ide-cel and tisa-cel showed a numerical but non-significant reduction in IP days. Of patients receiving OP liso-cel, cilta-cel, and tisa-cel, 47%, 20%, and 45% respectively did not require hospitalization in the first 30 days. Only 1 OP patient had grade 3 CRS. 48 pts completed OP BITE SUD (teclistamab: 37, talquetamab: 9, elranatamab:2; 1 pt. received prophylactic tocilizumab). 46% of patients had toxicity events (CRS: 44%, ICANS: 4%). All CRS events were grade 1-2 and ICANS grade 1, only one pt had recurrent CRS. The majority of pts with CRS were treated with tocilizumab, and hospitalized patients could receive the next SUD dose IP. For all 48 pts, there were a total of 72 IP days (mean, 1.5d/pt), compared to an estimated 282d of drug-specific monitoring periods. Notably, 54% of patients completed SUD without any hospitalization. Conclusions: Our outpatient T-cell redirecting therapies model significantly reduced inpatient utilization for both CAR-T and BiTE patients, leading to healthcare resource savings and improved patient experiences. No adverse safety events or clinically significant delays in care were associated with outpatient administration. Our model relies on robust patient and caregiver education, real-time provider communication, and relatively minor infrastructure and administrative adjustments—making it both safe and feasible for adoption by other centers.