CELL INTELLIGENCE · 肿瘤细胞治疗研究

Tisagenlecleucel (Kymriah), a CD19-directed CAR T-cell therapy, has demonstrated high efficacy in adolescents and young adults (AYA) with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, data from regions such as the Middle East, Southeast Asia, and Africa remain limited. Our center, based in Saudi Arabia, has been administering Tisagenlecleucel since March 2021. In this study, we retrospectively report on both clinical outcomes and the relationship between product characteristics, toxicity profiles, and treatment response in a real-world cohort of AYA patients.

We retrospectively analyzed data from 20 patients aged 14-25 years treated with Tisagenlecleucel between March 2021 and August 2024. Baseline characteristics, response rates, relapse-free survival (RFS), overall survival (OS), and toxicity data were collected. In addition, CAR T-cell product parameters, including cell composition and in-process metrics, were correlated with clinical efficacy and toxicity. Toxicities assessed included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and corticosteroid use.

The median age of the cohort was 19 years. By day 28 postinfusion, 89% of patients achieved complete remission. At a median follow-up of 12 months, the 1-year RFS and OS rates were 56% and 74%, respectively. B-cell aplasia loss occurred in 35% of patients at a median of 5 months, and 35% proceeded to allogeneic stem cell transplantation following CAR T-cell therapy. Grade III-IV CRS occurred in one patient (5%), and grade III-IV ICANS in two patients (10%). Exploratory analysis revealed associations between CAR T-cell product quality and both response and durability of remission. Additionally, steroid administration for toxicity management did not appear to compromise treatment efficacy.

This is the first report from Saudi Arabia evaluating Tisagenlecleucel outcomes in AYA patients with relapsed/refractory B-ALL. Our data confirm favorable response and survival rates consistent with international experience. Moreover, product quality metrics and toxicity management strategies may influence treatment durability, underscoring the need for region-specific real-world evidence to inform CAR T-cell therapy optimization.