Circulating CAR T-Cells After Treatment With Axicabtagene Ciloleucel in Patients With Relapsed/Refractory Aggressive...

This study investigates the expansion of CAR T-cells and its association to treatment outcome.

Patients with aggressive B-cell lymphomas treated with anti-CD19 CAR T-cell therapy axicabtagene ciloleucel (axi-cel) at Skåne and Sahlgrenska University Hospitals from 2019 to October 2024 were included. CAR T-cells in peripheral blood were measured by flow cytometry. Association between maximum levels of CAR T-cells and response, progression-free survival, overall survival, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were investigated.

Peak CAR T-cell levels were higher among patients with complete response (CR) at Day 30 (p = 0.013) and at 12 months (p = 0.036). CD8⁺ CAR T-cells were higher in patients with CR (median 135.7, IQR 52.8-433.9) compared to patients not obtaining CR (median 23.2, IQR 11.1-103.3) (p = 0.003). The ratio of CD4⁺:CD8⁺ CAR T-cells was lower in patients obtaining CR (p = 0.046). Patients with CAR T-cells above 52.4 CAR T-cells/μL showed superior progression-free survival (p < 0.001).

Our study indicates that CAR T-cell levels after axi-cel correlate to durable response, progression-free survival, and that expansion of CD8⁺ CAR T-cells might be of specific importance for efficacy. Potentially, CAR T-cell levels may be used to enable early detection of patients with high risk of CAR T-cell treatment failure.