Prognostic factors and outcomes of tisagenlecleucel in relapsed or refractory B-cell malignancies: a single-center...

Tisagenlecleucel (tisa-cel), a CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy, is an approved treatment for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and B-cell precursor acute lymphoblastic leukemia (B-ALL). While pivotal trials demonstrated its efficacy, real-world evidence from Asian populations remains scarce. In particular, data on manufacturing feasibility, clinical outcomes, and predictive biomarkers in Korean patients are limited.

This study aimed to evaluate the clinical outcomes and prognostic factors of tisa-cel therapy in Korean patients with R/R DLBCL and B-ALL, with a specific focus on apheresis product quality and baseline immune markers.

A single-center retrospective study was conducted including 91 patients (DLBCL = 72; B-ALL = 19) intended to receive tisa-cel between April 2022 and April 2024. Apheresis data, treatment responses, survival outcomes, and toxicity profiles were analyzed. The intention-to-treat (ITT) cohort was defined from the time of apheresis. Cox regression was used to identify predictors of survival and relapse, and separate analyses were performed for DLBCL and B-ALL.

Out of 91 patients, 72 received tisa-cel infusion. One-year overall survival (OS) and disease-free survival (DFS) for the entire ITT cohort were 45.9% and 37.5%, respectively. In 19 B-ALL after tisa-cel infusion, 1-year OS and DFS were 68.4% and 52.6%, with no non-relapse mortality (NRM). In 53 DLBCL after tisa-cel infusion, 1-year OS and DFS were 46.8% and 41.6%, respectively, with 29.6% cumulative incidence of relapse among responders. NRM was 9.5% mostly observed in elderly patients. In the DLBCL subgroup, poor OS was independently associated with third-or-later-line salvage therapy (hazard ratio [HR] 2.39), high peripheral blood monocyte proportion at apheresis (>10%, HR 2.57), low CD3+ T-cell concentration in apheresis product (<1.0×10⁸/mL, HR 4.31), and occurrence of immune effector cell-associated neurotoxicity syndrome (HR 2.47). B-ALL patients demonstrated favorable survival and lower toxicity, but no significant prognostic markers were identified.

Tisa-cel therapy was feasible and effective in Korean patients with R/R B-cell malignancies. Pre-treatment immune parameters such as monocyte burden and CD3+ T-cell quality in apheresis products significantly influenced outcomes in DLBCL. These findings suggest that optimizing patient selection and refining manufacturing strategies may enhance CAR-T efficacy, particularly in resource-constrained or heterogeneous real-world settings.