Hanajiri Ryo, Wakabayashi Hiroya, Ishigiwa Kohei, Ohara Fumiya, Hirano Shiho, Yokota Hirofumi, Kuwano Shihomi, Furukawa Katsuya, Shimada Kazuyuki, Sato Takahiko, Terakura Seitaro, Kiyoi Hitoshi
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Br J Haematol. 2025 Jul;207(1):180-188. doi: 10.1111/bjh.20186. Epub 2025 May 25.
Historically, the presence of measurable disease has been considered essential to stimulate CAR T-cell expansion and persistence. However, the kinetics of CAR T cells in patients achieving complete response (CR) before infusion remain poorly understood. This study aimed to evaluate the outcomes and CAR T-cell kinetics in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients stratified by pre-infusion disease status. In this retrospective analysis of 87 patients treated at a single institution, 23 (26.4%) were in CR and 64 (73.6%) were in non-CR prior to CAR T-cell infusion. Patients in CR exhibited significantly better progression-free survival (PFS) and overall survival compared to non-CR patients. Peripheral blood CAR T-cell kinetics, including the proportion and absolute counts of CAR T cells, CD4+ CAR T cells and CD8+ CART cells, showed no significant differences between CR and non-CR groups. These findings were consistent across different CAR T-cell products, whether 4-1BB- or CD28-based. Moreover, an analysis of patients achieving complete metabolic response (CMR) by PET-CT confirmed comparable CAR T-cell expansion and persistence in both CMR and non-CMR patients. Our findings demonstrate that CAR T-cell therapy achieves robust expansion and favourable survival outcomes in CR patients, even in the absence of measurable disease.
从历史上看,可测量疾病的存在一直被认为是刺激CAR T细胞扩增和持续存在的必要条件。然而,对于在输注前达到完全缓解(CR)的患者中CAR T细胞的动力学仍知之甚少。本研究旨在评估根据输注前疾病状态分层的复发/难治性弥漫性大B细胞淋巴瘤(DLBCL)患者的预后和CAR T细胞动力学。在对一家机构治疗的87例患者进行的这项回顾性分析中,23例(26.4%)在CAR T细胞输注前处于CR状态,64例(73.6%)处于非CR状态。与非CR患者相比,CR患者表现出显著更好的无进展生存期(PFS)和总生存期。外周血CAR T细胞动力学,包括CAR T细胞、CD4+ CAR T细胞和CD8+ CAR T细胞的比例和绝对计数,在CR组和非CR组之间没有显著差异。无论基于4-1BB还是CD28,这些发现对于不同的CAR T细胞产品都是一致的。此外,对通过PET-CT达到完全代谢缓解(CMR)的患者的分析证实,CMR患者和非CMR患者的CAR T细胞扩增和持续存在情况相当。我们的研究结果表明,即使在没有可测量疾病的情况下,CAR T细胞疗法在CR患者中也能实现强劲的扩增和良好的生存结果。