Real world chimeric antigen receptor T-cell therapy outcomes in T cell/histiocyte-rich large B-cell lymphoma: The Australian experience

Abstract Background: T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) poses significant therapeutic challenges in the relapsed/refractory (R/R) setting. Despite the growing utilisation of CD19-directed chimeric antigen receptor T-cell (CAR-T), data on its efficacy and safety in THRLBCL remain limited. Here we report on the Australian CAR-T outcomes for R/R THRLBCL. Methods: This retrospective study included adult patients (pts) with R/R THRLBCL from 2020 to 2025 from 6 Australian centres. Pts received commercial CD19-directed CAR-T cell therapy; Axicabtagene ciloleucel (Axi-cel) or Tisagenlecleucel (Tisa-cel). Patient, disease, and treatment characteristics were collated and analysed. Lymphoma response assessment was by Lugano criteria and survival outcomes according to Kaplan-Meier methodology. Results: Eleven pts underwent leukapheresis and were eligible for analysis; with 10 pts proceeding to CAR-T infusion. The median age of the cohort was 67 years with a male predominance (89%). 50% had primary refractory disease with 80% refractory to ≥2 prior therapies. 20% were post-ASCT. Axi-cel was infused in 80% and Tisa-cel in 20%. Bridging therapy was administered in 70% of pts, comprising checkpoint inhibitor 10%, immunochemotherapy 20%, corticosteroids-only 10%, polatuzumab 10% and radiotherapy 20%. The overall response rate at day 30 was 67%, with a complete response rate of 56% and a partial response rate of 11%.The 1-year progression-free survival was 44% (57% for Axi-cel and 0% for Tisa-cel) and 1-year overall survival was 57% (60% for Axi-cel and 50% for Tisa-cel). Cytokine release syndrome of any grade occurred in 60% (grade ≥3 in 0%) and any-grade immune effector cell-associated neurotoxicity syndrome in 40% (grade ≥3 in 10%), with 20% requiring ICU admission. Conclusions: Despite the small sample size, our findings indicate that CD19-directed CAR T-cell therapy demonstrates encouraging efficacy and manageable toxicity in R/R THRLBCL. Further large-scale prospective studies are warranted to validate these results and refine therapeutic strategies.