Prophylactic Corticosteroids Allow Safe Outpatient Administration of Axicabtagene Ciloleucel with Comparable Toxicities to Other CAR-T Therapies in Large Cell Lymphoma

Chimeric Antigen Receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating certain hematologic malignancies, particularly in relapsed or refractory non-Hodgkin Lymphomas (r/r NHL). Currently, there are five FDA-approved CAR-T therapies for r/r NHL. These therapies have produced durable responses and sometimes put r/r NHLs into complete remission. However, CAR-T therapies are frequently associated with severe adverse effects, including Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), often leading to lengthy hospitalizations and significant morbidity and mortality. Prophylactic regimens have been developed to reduce the risk of CRS and ICANs.

We have performed a retrospective cohort study comparing outpatient administration of axicabtagene ciloleucel combined with our steroid-based prophylactic regimen (n=40) to Lisocabtagene maraleucel (n=47) and Tisagenleleucel (n=28) therapies in patients with r/r NHL receiving outpatient CAR-T therapy between January 2018 and March 2024. Patients were admitted on the day of cell therapy infusion and discharged the same day. Admissions were reserved for complications requiring inpatient care. Dexamethasone 10mg was started on day 0 through day 2 for patients receiving axicabtagene. Our population consisted of self-identified White, Black/African American, Asian, Native American/Alaskan, or declined (78%, 14.6%, 4.8%, 1.6%, 1.0%). All patients were risk-stratified before CAR-T infusion. Every patient was assessed for CRS and ICANS for the duration of their treatment. Patients who developed CRS or ICANS were graded using the American Society for Transplantation and Cellular Therapy (ASTCT) and Immune Effector Cell–Associated Hematotoxicity (ICAHT) standardized grading systems, respectively. Primary outcome measures were max grade CRS, max grade ICANS, number of days with absolute neutrophil count ≤ 500 cells/µL, number of days platelet ≤20K/µL, number of admissions to the hospital, hospital length of stay (days), day 100 disease status, and overall survival. All statistical analyses used alpha levels of 0.05 and 95% confidence intervals.

Of the 115 CAR-T infusions, 71 patients (61.7%) developed CRS, and 40 patients (34.7%) developed ICANS during treatment. The incidence of CRS by grade in the investigational and control group was: grade 1 (n=16, 40%; n=25, 32.8%), grade 2 (n=16, 40%; n=9, 11.8%), grade 3 (n=0, 0%; n=2, 2.6%), grade 4 (n=2, 5%; n=1, 1.4%), respectively (P=0.232). The incidence of ICANS by grade in the investigational and control group was: grade 1 (n=6, 15%; n=10, 13.15%), grade 2 (n=1, 2.5%; n=6, 7.8%), grade 3 (n=11, 27.5%; n=4, 5.26%), grade 4 (n=1, 2.5%; n=1, 2.5%), respectively (P=0.076). The mean number of days with ANC ≤ 500 cells/µL was 17.65 CI [11.56, 23.73] in the investigational group and 9.0 CI [6.52, 11.47] for the control (P=0.012). The mean number of days with platelet count ≤ 20K/µL was 22.65 CI [12.51, 32.78] in the investigational group and 6.89 CI [2.56, 11.21] in the control (P=0.007). The mean hospital length of stay (days) for the investigational group was 12.94 CI [7.96, 17.92] and 7.99 CI [5.79, 10.18] for the control (P=0.077). The mean number of hospitalizations for the investigational group was 1.9 CI [1.60, 2.19] and 2.05 CI [1.70, 2.35] for the control (P=0.497). The investigational and control groups had a day 100 disease status of complete remission (42.5%; 30.0%), partial remission (10.0%; 8.0%), stable (2.5%; 4.0%), progression (15.0%; 13.0%), relapsed (10.0%; 5.0%), deceased (7.50%; 28.0%), and no status (12.5%; 12.0%). The overall survival of the investigational and control groups was 60% (n=24) and 50.6% (n=38), respectively (P=0.343).

Our data shows no statistical difference between the experimental and control groups in the max grade CRS, max grade ICANS, number of hospitalizations, and hospital length of stay. This indicates that the prophylactic regimen used with outpatient axicabtagene ciloleucel achieved similar toxicity profiles and hospitalization statistics compared to the standard treatments.