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. 2025 Mar 17;32(3):173.
doi: 10.3390/curroncol32030173.

Enhancing CAR-T Efficacy in Large B-Cell Lymphoma with Radiation Bridging Therapy: A Real-World Single-Center Experience

Eva Laverdure  1   2   3 , Luigina Mollica  1   3 , Imran Ahmad  1   3 , Sandra Cohen  1   3 , Silvy Lachance  1   3 , Olivier Veilleux  1   3 , Maryse Bernard  3   4 , Eve-Lyne Marchand  3   4 , Jean-Sébastien Delisle  1   3 , Lea Bernard  1   3 , Mélissa Boileau  1   3 , Tony Petrella  3   5 , Sarah-Jeanne Pilon  3   5 , Philippe Bouchard  6 , Denis-Claude Roy  1   3 , Lambert Busque  1   3 , Isabelle Fleury  1   3
Affiliations

Enhancing CAR-T Efficacy in Large B-Cell Lymphoma with Radiation Bridging Therapy: A Real-World Single-Center Experience

Eva Laverdure et al. Curr Oncol. .

Abstract

One challenge of chimeric antigen receptor T-cell therapy (CAR-T) for relapsed or refractory large B-cell lymphoma (LBCL) is achieving disease control during manufacturing. We report real-word outcomes of 100 patients treated with axicabtagene ciloleucel (axi-cel, n = 50) or tisagenlecleucel (tisa-cel, n = 50) at our center. Most patients received bridging therapy (BT) with 48 undergoing radiation BT (RBT) and 32 receiving systemic BT (SBT). The best overall response rate (ORR) was 84% (78% complete response (CR)) for axi-cel and 60% (42% CR) for tisa-cel. At a median follow-up of 16 months, 12-month progression-free survival (PFS) and overall survival (OS) were 72% and 82% for axi-cel, compared to 35% and 57% for tisa-cel. By the bridging approach, 12-month PFS was 60% with RBT, 59% without BT and 35% with SBT (p = 0.06). Notably, axi-cel patients without lymphoma progression during manufacturing (n = 24) achieved 12-month PFS and OS rates of 91% and 96%, respectively. Axi-cel was associated with more cytokine release syndrome (92% vs. 66%, p = 0.003) and neurotoxicity (all-grade 56% vs. 10%, p < 0.001, grade ≥ 328% vs. 4%, p = 0.002). Multivariate analysis identified RBT as independently associated with improved PFS (HR 0.46, 95% CI 0.22-0.96). Pending prospective validation, RBT shows promise for improving CAR-T outcomes in LBCL.

Keywords: CAR-T; bridging therapy; large B-cell lymphoma; radiation therapy.

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Conflict of interest statement

E.L.: Consultancy for AbbVie, AstraZeneca, Gilead, and Incyte. I.F.: Consultancy for AbbVie, AstraZeneca, Beigene, Celgene, Gilead, Incyte, Janssen, Merck, Novartis, Roche, and Seagen; speaker bureau for AbbVie, Beigene, Gilead, Incyte, and Seagen. I.A.: Consultancy for AbbVie, Genentech, Incyte, Jazz Pharmaceuticals, Medexus, Sanofi, and Vertex Pharmaceuticals. S.C.: Consultancy for ExCellThera and Sanofi. S.L.: Consultancy for Jazz Pharma, Gilead, Novartis, Sanofi, and Merck; patent holder and potential royalties from sales of UM171; speaker bureau for Jazz Pharma and Novartis. O.V.: Honoraria for Gilead, Novartis, AbbVie, and Sanofi; consultancy for Gilead and AbbVie. E.M.: Consultancy and patent holder for AFX medical. J.-S.D.: Consultancy for Vertex Pharmaceuticals; patent holder for Université de Montréal; member of the Medical and Scientific Board of Leukemia/Lymphoma Society of Canada, Héma-Québec. L. Bernard: Consultancy for Bristol-Mayer-Squibb. P.B.: Consultancy for BMS-Celgene. D.-C.R.: Consultancy for CellProthera. L.B.: Advisory board for Novartis, BMS, Paladin, and Johnson & Johnson.

Figures

Figure 1
Figure 1
Progression-free survival according (a) to CAR-T (b) to bridging therapy. Abbreviations: PFS: progression-free survival; CAR-T: chimeric antigen receptor T-cell therapy; axi-cel: axicabtagene ciloleucel; tisa-cel: tisagenlecleucel.
Figure 2
Figure 2
Progression-free survival according to CAR-T and disease status at infusion. PFS: progression-free survival; CAR-T: chimeric antigen receptor T-cell therapy; axi-cel: axicabtagene ciloleucel; tisa-cel: tisagenlecleucel, PD: progressive disease prior lymphodepletion.
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