Impact of putative cell of origin on CD19+CAR-T outcomes in patients with large B-cell lymphoma

作者：Muhammad Bilal Abid, Lei Feng, Amy Ayers, Veronica Leautaud, Paolo Strati, Luis Fayad, Loretta J. Nastoupil, Ranjit Nair, Maria Alma Rodriguez, Swaminathan P. Iyer, Partow Kebriaei, Elizabeth J. Shpall, Jeremy Ramdial, Farzaneh Maadani, Fateeha Furqan, Chijioke Nze, Preetesh Jain, Hun Ju Lee, Luis Malpica, Amrita Chauhan, Michael Wang, Jason R. Westin, Christopher R. Flowers, Sattva S. Neelapu, Sairah Ahmed · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-5500 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Lymphoma Diagnosis and Treatment、Cutaneous lymphoproliferative disorders research

Abstract Background CAR-T therapy has demonstrated improved survival in patients with relapsed, refractory large B cell lymphoma (R/R LBCL). While the putative cell of origin (COO) (germinal center B-cell [GCB] vs non-GCB) impacts prognosis and treatment responses in LBCL as well as with autoHCT (Iqbal et al. CLML 2022), the impact of COO on CAR-T outcomes remains elusive. Additionally, while survival following axi-cel therapy (CAR-T in second line) was prolonged compared to SOC for both COO subtypes, the studies were not designed to detect differences in outcomes based on COO (Locke et al. NEJM 2022). Methods In this retrospective analysis, we examined the impact of COO in patients with LBCL receiving commercial CD19+CAR-T between April 2019 and October 2024, stratified by lines of therapy (LOT; 2L vs 3L+). Axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) were included in 2L and axi-cel, liso-cel and tisagenlecleucel (tisa-cel) in third-line and beyond (3L+) setting. COO stratification was based on Hans algorithm (Hanset al. Blood 2004). Response to CAR-T was assessed per Lugano PET/CT criteria. Progression-free survival (PFS) was the primary endpoint. Cox proportional hazards models were used for multivariable analysis. Results Of 344 patients, 59% (n=203) patients had GCB and 41% (n=141) had non-GCB subtype. Overall, 63.1% (n=217) patients received bridging and 99.4% (n=342) FluCy-based lymphodepletion. Axi-cel accounted for 79.1% (n=272) CAR-T, li...