Response‐adapted zanubrutinib and tislelizumab as a potential strategy to enhance CD19 CAR T‐cell therapy in relapsed/refractory large B‐cell lymphoma: A retrospective observational study

作者：Rong Shen, Weiguo Cao, Wang Li, Lingshuang Sheng, Yilun Zhang, Wen Wu, Pengpeng Xu, Shu Cheng, Meng‐Ke Liu, Yan Dong, Yue Wang, Xiangqin Weng, Xufeng Jiang, Qi Song, Hongmei Yi, Lei Li, Sheng Chen, Zi‐Xun Yan, Weili Zhao · 发表于：Clinical and Translational Medicine · 年份：2025 · DOI：10.1002/ctm2.70310 · 被引用次数：4 · 研究领域：CAR-T cell therapy research、Lymphoma Diagnosis and Treatment、Cutaneous lymphoproliferative disorders research

BACKGROUND: CD19 chimeric antigen receptor (CAR) T-cell therapy is a potential treatment for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The combination of targeted therapeutic strategies, particularly bruton tyrosine kinase inhibitor zanubrutinib and programmed death-1 inhibitor tislelizumab, may improve clinical outcomes and modulate the tumour microenvironment (TME). METHODS: We studied patients with R/R LBCL who received response-adapted zanubrutinib plus tislelizumab upon CD19 CAR T-cell therapy between June 2021 and March 2023. Patients were treated with zanubrutinib daily from leukapheresis to day 28 post-infusion; those achieving complete response continued zanubrutinib monotherapy for 3 months, while partial responders received combined zanubrutinib for 3 months and tislelizumab for up to 2 years. We evaluated the overall response rate (ORR), complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and safety. DNA sequencing and RNA sequencing were performed on available tumour samples to analyse genetic aberrations and TME characteristics. RESULTS: A total of 54 patients with LBCL were included, with a median follow-up of 23.6 months. The ORR at day 28, month 3, and month 6 were 94% (CRR 66%), 87% (CRR 80%), and 80% (CRR 76%), respectively. The 2-year PFS and 2-year OS rates were 68% and 76%, respectively. Median PFS and median OS were not reached. Grade ≥ 3 cytokine release syndrome occurred in 9% of patients, with no grade ...