Long-term Outcomes and Immune Reconstitution after Tisagenlecleucel in Relapsed or Refractory Large B-cell Lymphoma: A Single-institution Retrospective Study in Japan with Over 3 years Follow-up

Background Tisagenlecleucel (tisa-cel) is a CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory (r/r) large B-cell lymphoma (LBCL). However, real-world long-term outcomes in Japanese populations remain limited. Methods We retrospectively analyzed patients with LBCL who underwent leukapheresis for tisa-cel between April 2020 and July 2022 at the National Cancer Center Hospital (NCCH), Tokyo. Efficacy, survival, and immune reconstitution data were collected through December 2024. Results Among 24 patients who underwent leukapheresis, 21 received tisa-cel infusion. The median follow-up among survivors was 3.2 years (range, 0.2–4.3). The overall response rate (ORR) was 61.9% at 1 month and 52.4% at 3 months. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 62.2% and 42.9%, respectively. CD4⁺ T-cell depletion (CD4⁺ T-cell < 200 cells/µL) persisted in 30.0% of complete response (CR) survivors at 1 year; however, all patients recovered at 3 years. In contrast, CD19⁺ B-cell reconstitution remained limited, with B-cell aplasia observed in 70.0% of CR survivors at 1 year and 66.7% at 3 years. In addition, hypogammaglobulinemia (IgG < 400 mg/dL) persisted in 57.1% of CR survivors at 3 years, indicating sustained impairment of humoral immunity. Conclusions Tisa-cel demonstrated sustained long-term efficacy in Japanese patients with LBCL in a real-world setting. However, prolonged B-cell aplasia and persistent hypogammaglobulinemia were frequently observed, highlighting the importance of long-term immune monitoring and infection prevention strategies after CAR T-cell therapy.