Outpatient Administration of Commercial antiCD19 and Antibcma Chimeric Antigen Receptor-Modified T-Cell (CAR-T) Therapies Using a Strategy of No Remote Monitoring and Early Cytokine Release Syndrome (CRS) Intervention

Introduction Recent studies have shown feasibility of outpatient (OP) CAR-T administration. However, most studies employed a resource intensive at home monitoring system, while others restricted it to CARs with 41BB costimulatory domains. We report outcomes of OP administration of CD19- or BCMA-directed commercial CAR-T therapy without remote at home monitoring and using an early CRS intervention strategy. Methods All adult patients with hematologic malignancies receiving a commercial CAR-T therapy during 2022-23 were managed in the OP setting, except those with active central nervous system (CNS) disease, hemodialysis and acute lymphoblastic leukemia (ALL) (ALL was allowed after 6/2023). No remote monitoring of vital signs or symptoms was performed. Patients were seen daily in the CAR-T center day hospital (DH) for the first 7-10 days and then twice weekly through day 30. Early CRS intervention involved administering tocilizumab (Toci) as OP (in DH during the daytime or OP 24-hour Clinic at nighttime) for grade ≥1 CRS. Patients were admitted if they had Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), neutropenic fever or hemodynamic instability. Results Forty-eight patients received commercial CAR-T infusion in the OP setting, including 30 myeloma (MM), 17 lymphoma (LYM) and 1 ALL patient (Table 1). Infused products included all commercially available CAR-T constructs (Table 1). 31 (64%) out of 48 OP CAR-T patients were hospitalized in the first 30 days. The median interval between CAR-T infusion and hospitalization was 4 (range: 0-22) days. Median length of hospitalization was 3 (1-14) days. The distribution of admissions during days 0-3 vs. days 4-7 vs. day 8-30 post CAR-T was 11 patients (23%; 6 MM=6; LYM=5) vs. 14 patients (29%; MM=7, LYM=6, ALL=1) and 6 patients (13%; MM=5, LYM=1), respectively. The most common reason for admission was CAR-T toxicities (21/31): CRS (13), ICANS (4), and both (4). CRS occurred in 35 (73%) patients; all grade 1-2. Hospitalization for CRS was prevented in 7 patients with OP Toci administration while 11 were admitted for persistent CRS despite OP Toci. ICANS occurred in 10 (20%) patients, including 4 (8%) grade 3-4. The overall response rate (ORR) was 67% (CR=8, PR=2) and 76% (CR=19, VGPR/PR=3) respectively in the 15 evaluable patients with lymphoma and 29 with MM. After a median follow up of 7 months, 11 patients (7 lymphoma, 4 MM) died (10 progression, 1 ICANS). The median progression free and overall survivals were 4.6 and 9.1 months in LYM and 12.8 months and not reached in MM respectively. The non-relapse mortality rates were 0% at 1 months and 2% at 6 months. Conclusion Commercial antiCD19 and antiBCMA CAR-T therapies are feasible to administer in OP setting using a strategy of no remote monitoring and early CRS intervention. This strategy is associated with reduced IP resource utilization and favorable outcomes.