Austrian Real-world Experience With Standard of Care Brexucabtagene Autoleucel in Patients With Relapsed or...

Mantle-cell lymphoma (MCL) represents a rare B cell malignancy with a challenging treatment situation in the case of relapsed or refractory (r/r) disease. Brexu-cel as first approved chimeric antigen receptor T cell (CART) therapy revolutionized the therapeutic landscape and outcome in r/r MCL patients. This retrospective study analyzes the real-world data of patients with r/r MCL enrolled into the CART program in Austria. In total, 33 patients in Austria were analyzed from 2021 to January 2025. Inclusion criteria comprised confirmed diagnosis of r/r MCL, an age ≥18 years and a confirmed enrollment into the CART program. Primary endpoints were the overall response rate (ORR), overall survival (OS) and progression-free survival (PFS). Further endpoints included the incidence and severity of CART-specific adverse events (AE) such as the cytokine-release-syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS). Of all 33 patients enrolled into the CART program, 24 patients (72.7%) were treated with brexu-cel whereas 9 patients (27.3%) received alternative treatments. Most common cause for alternative treatment was disease progression. The ORR for brexu-cel was 95.9%, with a 2-year OS- and PFS rate of 76.8% and 50.8%, respectively. In the alternative treatment group, the 2-year OS and PFS rates were 13.9% and 18.5%. Grade ≥2 CRS and ICANS occurred in 62.5% and 37.5%, respectively. There were no Grade 5 adverse events related to brexu-cel. Patients with a leukocyte count >4.1 G/L at the time point of lymphodepletion had a significantly higher incidence of CRS grade ≥2, whereas a neutrophil count ≥4.75 G/L at the time point of lymphodepletion was associated with a higher incidence of ICANS grade ≥2. Our study provides first insights into the real-world trajectories and outcomes of r/r MCL patients intended for brexu-cel treatment in Austria. This analysis confirms the high rates of ORR and OS of Brexu-cel in MCL also in the real-world setting. Exploratory analysis suggested that increased leukocyte and neutrophil counts at lymphodepletion may be associated with increased risk of CRS and ICANS, respectively.