Outcomes of tisagenlecleucel versus allogeneic hematopoietic stem cell transplantation in relapsed or refractory large B-cell lymphoma.

[BACKGROUND] CD19-targeted chimeric antigen receptor (CAR)-T cell therapy has changed third-line treatment for relapsed/refractory large B-cell lymphoma (r/r LBCL). However, whether CAR-T therapy outperforms allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. The aim of this study was to compare the real-world outcomes of tisagenlecleucel (Tisa-cel) CAR-T therapy versus allo-HSCT in adults with r/r LBCL, with a focus on survival, relapse, and nonrelapse mortality (NRM).

[METHODS] We conducted a retrospective analysis of adult patients treated with Tisa-cel (June 2022-October 2024) or allo-HSCT (April 2012-June 2023) at two Korean centers. Optimal cut-off points for continuous variables were determined using a survival-tree algorithm. Patient characteristics, overall survival (OS), progression-free survival (PFS), cumulative relapse, and NRM were compared between groups.

[RESULTS] In total, 127 patients were included (74 Tisa-cel, 53 allo-HSCT). Patients in the Tisa-cel group were older (median age of 61 versus 46 years) and had a higher proportion of high-risk disease than those in the allo-HSCT group. At 12 months, OS and PFS were similar between the two groups: OS was 50.1% and 45.3% with Tisa-cel and allo-HSCT (P = 0.784), respectively, and PFS was 40.8% and 35.9% (P = 0.819), respectively. NRM was significantly lower with Tisa-cel than with allo-HSCT (P = 0.009), although the cumulative incidence of relapse rates was similar (P = 0.066). Multivariable analysis identified poor response to bridging chemotherapy and refractory disease as predictors of inferior OS in both groups. An interval of less than 18 months from diagnosis to second relapse was independently associated with worse OS and PFS and a higher risk for relapse after allo-HSCT (P < 0.001); nonetheless, it did not affect outcomes after Tisa-cel therapy. The median OS for patients experiencing a relapse within 18 months was 9.5 months with Tisa-cel and 4.7 months with allo-HSCT. The poorer survival in the allo-HSCT group was primarily influenced by excess NRM.

[CONCLUSIONS] Tisa-cel provides disease control comparable to allo-HSCT while markedly reducing NRM, resulting in a clear survival advantage when relapse occurs within 18 months of diagnosis. These real-world data support the earlier use of CAR-T therapy in the treatment course for high-risk r/r LBCL.