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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Hematologic Malignancies

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1633644

Real-World Australian Experience With Tisagenlecleucel for Relapsed/Refractory Diffuse Large B-Cell Lymphoma -Importance of Pre-CAR-T Optimization

Provisionally accepted
Phoebe Joy  HoPhoebe Joy Ho1,2*Vinay  VanguruVinay Vanguru2,3Cale  S BurgeCale S Burge3Rebecca  WayteRebecca Wayte2,3Christina  BrownChristina Brown2,3Christian  E BryantChristian E Bryant2,3Scott  DunkleyScott Dunkley2,3Derek  McCullochDerek McCulloch2,3Liane  KhooLiane Khoo2,3James  FavaloroJames Favaloro3Anthony  JeffreyAnthony Jeffrey2,3Annie  SolterbeckAnnie Solterbeck4Stephen  LarsenStephen Larsen2,3Edward  AbadirEdward Abadir2,3
  • 1Royal Prince Alfred Hospital, Sydney, Australia
  • 2University of Sydney, Sydney, Australia
  • 3Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  • 4Statistical Revelations, Ocean Grove, Victoria, Australia

The final, formatted version of the article will be published soon.

Introduction: Up to 50% of patients with diffuse large B-cell lymphoma (DLBCL) relapse or are refractory to first-line therapy. Tisagenlecleucel, a CD19-directed chimeric antigen receptor (CAR)-T cell therapy, is approved for patients with relapsed/refractory (r/r) DLBCL in the third-line setting. Patients with r/r DLBCL treated with tisagenlecleucel in the real world have shown similar outcomes to those in clinical trials.We report a single-center real-world analysis of patients with r/r DLBCL treated with tisagenlecleucel.Results: As of December 31, 2024, 63 patients with r/r DLBCL had received tisagenlecleucel (median follow-up 15 months). Cytokine release syndrome occurred in 89%; 95% were grade 1/2. Immune effector cell-associated neurotoxicity syndrome was reported in 17% (10/11 cases mild; 1 case grade ≥3). Overall response rate was 79%, with 60% complete response (CR). Median duration of response was 26.4 months. Median progression-free survival (PFS) was 14.6 months and overall survival (OS) was 15.4 months. Patients whose response at day 30 was CR had a 42% reduction in risk of progression compared with those who achieved partial response (PR). High lactate dehydrogenase (LDH) at infusion was associated with a higher risk of disease progression (hazard ratio [HR] 2.1) and death (HR 2.65) than normal LDH, with the risk for progression increased 3.3fold in a multivariate model. Almost one third of our patients who achieved CR had normalized their LDH at the time of infusion from a previously elevated level, of whom 87% (13/15) had received bridging therapy. Lack of response to bridging was associated with an almost 2-fold increased risk of progression compared with responsive patients (3.1 vs 19.5 months; HR 1.9; 95% CI: 0.9-3.9, P=0.08).We demonstrated in this analysis that the safety and efficacy of tisagenlecleucel in patients with r/r DLBCL in an Australian real-world setting were better than in the pivotal JULIET clinical trial and other registry studies. We also confirmed the importance of achieving early CR and normalizing LDH levels at CAR-T cell infusion to reduce the risk of disease progression. Our results suggest that bridging therapy played an important role in optimizing outcomes by managing pre-CAR-T disease control.

Keywords: Min. 5-Max. 8): r/r DLBCL, car-t, Real-world, tisagenlecleucel, Relapsed, Refractory

Received: 23 May 2025; Accepted: 21 Jul 2025.

Copyright: © 2025 Ho, Vanguru, Burge, Wayte, Brown, Bryant, Dunkley, McCulloch, Khoo, Favaloro, Jeffrey, Solterbeck, Larsen and Abadir. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Phoebe Joy Ho, Royal Prince Alfred Hospital, Sydney, Australia

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