Can modified lymphodepletion before tisagenlecleucel improve outcome in high-risk patients with large B-cell lymphoma?

作者：Marta Canelo-Vilaseca, Mohamad Sabbah, Caterina Cristinelli, Bommier Côme, Pierre Sesques, Mikaël Roussel, Pierre Bories, Vincent Allain, Amani Ouedrani, Ilenia De Bernardis, Agathe Vély, Pierre Stéphan, L. Vercellino, Fabienne Venet, Rémi Pescarmona, Roch Houot, François Vergez, Romain de Jorna, Isabelle Madelaine, Nathalie Parquet, Anne Brignier, J. Larghero, Miryam Mebarki, Roberta Di Blasi, Sophie Caillat‐Zucman, Catherine Thieblemont · 发表于：Bone Marrow Transplantation · 年份：2026 · DOI：10.1038/s41409-025-02754-4 · 研究领域：CAR-T cell therapy research、Lymphoma Diagnosis and Treatment、Acute Lymphoblastic Leukemia research

Lymphodepletion (LD) is a critical component of chimeric antigen receptor T-cell (CAR T-cell) therapy, maximizing the engraftment, efficacy and long-term survival of infused cells [ 1 ]. Although these drugs provided a therapeutical breakthrough, notably in patients with non-Hodgkin lymphoma (NHL), less than half of them achieve a durable response and the prognosis of post CAR T-cell relapse is very poor [ 2 , 3 ]. Mechanisms contributing to CAR T-cells treatment failure include disease-related characteristics (total metabolic tumor volume [TMTV], lactate dehydrogenase [LDH] and C-reactive protein levels, performance status and targeted antigen loss), as well as CAR T-cell-related factors (poor T-cell fitness, T-cell exhaustion, lack of persistence and type of costimulatory molecules in the CAR construct) [ 1 ].