Axicabtagene ciloleucel shows higher early response but greater toxicity than tisagenlecleucel in large B-cell lymphomaComparison of two CAR-T cell therapies for lymphoma

BACKGROUND AND OBJECTIVES: Large B-cell lymphoma (LBCL) is a common and aggressive non-Hodgkin lymphoma (NHL) characterized by abnormal proliferation of mature B lymphocytes, with a 10-year prevalence of up to 45 cases per 100,000 individuals in European populations and a continuing upward trend. Axicabtagene ciloleucel (Axi-cel) and Tisagenlecleucel (Tisa-cel) are the two most established chimeric antigen receptor T-cell (CAR-T) therapy products for LBCL, yet a systematic comparison of their efficacy and safety in European populations has been lacking. This systematic review and meta-analysis aims to address this gap by comprehensively evaluating differences in treatment efficacy and adverse events between Axi-cel and Tisa-cel in European patients with LBCL. MATERIALS AND METHODS: We searched PubMed, Cochrane Library, Scopus, and other databases for studies published between January 2020 and February 2026, ultimately including eight European cohort studies with a total of 2,178 patients. Efficacy and survival outcomes comprised 3-month overall response (OR), 3-month complete response (CR), 12-month progression-free survival (PFS), and 12-month overall survival (OS). Toxicity outcomes included 12-month non-relapse mortality (NRM), all-grade and grade ≥ 3 cytokine release syndrome (CRS), all-grade and grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS), all-grade and grade ≥ 3 neutropenia, thrombocytopenia, and anemia, as well as tocilizumab use and ICU support. A random-effects model was used for pooled analysis, with sensitivity analyses performed for outcomes exhibiting substantial heterogeneity. RESULTS: Regarding efficacy, Axi-cel was associated with significantly higher 3-month OR and 3-month CR rates compared with Tisa-cel, whereas 12-month PFS was lower in the Axi-cel group. In terms of toxicity, the incidences of all-grade CRS, all-grade ICANS, and grade ≥ 3 ICANS were significantly higher with Axi-cel, and tocilizumab use was more frequent. No statistically significant differences were observed for the remaining outcomes. CONCLUSIONS: In European patients with LBCL, Axi-cel demonstrated superior short-term efficacy compared with Tisa-cel, but showed inferior performance on certain intermediate-term efficacy endpoints and was generally associated with greater toxicity and higher healthcare resource utilization. Clinical selection of a CAR-T regimen should be individualized, with careful consideration of efficacy, toxicity, and cost. Future high-quality studies with longer follow-up are needed to evaluate long-term outcomes and to validate the findings of this analysis.