Clinical outcome and immunophenotype of axicabtagene ciloleucel (axi-cel) and relmacabtagene autoleucel (relma-cel) in relapsed/refractory large B-Cell lymphoma on Chinese population: a single-center experience.

Abstract

Background: Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has shown remarkable efficacy for treating relapsed or refractory (r/r) large B-cell lymphomas, leading to the approval of axicabtagene ciloleucel (axi-cel) and relmacabtagene autoleucel (relma-cel) in China. Despite these advances, limited real-world data exist for CAR-T therapies in Asian populations, and comparative outcomes between axi-cel and relma-cel remain understudied.

Methods: This retrospective cohort study analyzed real-world efficacy and safety data for commercial CD19 CAR-T therapies in 33 patients with r/r large B-cell lymphoma treated at a tertiary hospital in China. Baseline demographics, International Prognostic Index (IPI) scores, performance status, and genetic profiles were collected. Additionally, T-cell immunophenotypes were assessed in a subset of patients pre- and post-CAR-T manufacturing to evaluate potential associations with clinical outcomes. Clinical responses were measured using PET/CT, and survival was analyzed via Kaplan-Meier methods.

Results: Among the 33 patients (median age 53), 76.7% achieved a complete response (CR) three months post-CAR-T infusion. One-year overall survival (OS) was 72.3%, and the one-year progression-free survival (PFS) was 71.2%. T-cell phenotype analysis revealed no significant association between initial T-cell subsets and final CAR-T product characteristics. Axi-cel demonstrated a higher CR rate (100%) compared to relma-cel (61.1%) but was associated with more severe cytokine release syndrome (CRS). Patients with a higher proportion of stem-like memory T cells (CCR7 + CD45RA+) in the relma-cel product exhibited reduced efficacy, suggesting an optimal range of stem-like memory cell proportions for therapeutic benefit.

Conclusion: In this cohort, CAR-T therapies for r/r large B-cell lymphoma yielded high response rates and promising survival outcomes, with axi-cel showing superior efficacy but higher CRS incidence compared to relma-cel. The study highlights the need for optimal stem-like memory T-cell proportions in CAR-T products for improved efficacy. Prospective multicenter studies are warranted to confirm these findings in larger patient populations.