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侵袭性 B 细胞淋巴瘤中 axicabtagene-ciloleucel CAR T 细胞应答的预测因素:一项真实世界研究。

Predictors of response to axicabtagene-ciloleucel CAR T cells in aggressive B cell lymphomas: A real-world study.

机构信息

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Department of Medicine, University of Washington, Seattle, Washington, USA.

出版信息

J Cell Mol Med. 2022 Dec;26(24):5976-5983. doi: 10.1111/jcmm.17550. Epub 2022 Dec 1.

Abstract

Chimeric antigen receptor T-cell (CAR T) therapy has shown promising efficacy in relapsed and refractory diffuse large B cell lymphoma (DLBCL). While most patients undergo CAR T infusion with active disease, the impact of some clinical variables, such as responsiveness to the pre-CAR T chemotherapy on the response to CAR T, is unknown. In this single-institution study, we studied the impact of several pre-CAR T variables on the post-CAR outcomes. Sixty patients underwent apheresis for axicabtagene-ciloleucel (axi-cel) and 42 of them (70.0%) had primary refractory disease. Bridging therapy between apheresis and lymphodepletion was given in 34 patients (56.7%). After axi-cel, the overall response rate was 63.3%. Responsiveness to the immediate pre-CAR T therapy did not show a significant association with response to axi-cel, progression-free (PFS) or overall (OS) survival. Multivariable analysis determined that bulky disease before lymphodepletion was independently associated with inferior outcomes, and patients that presented with high-burden disease unresponsive to immediate pre-CAR T therapy had a dismal outcome. This data supports proceeding with treatment in CAR T candidates regardless of their response to immediate pre-CAR T therapy. Interim therapeutic interventions should be considered in patients who have known risk factors for poor outcomes (bulky disease, high LDH).

摘要

嵌合抗原受体 T 细胞(CAR T)疗法在复发/难治性弥漫性大 B 细胞淋巴瘤(DLBCL)中显示出良好的疗效。虽然大多数患者在有疾病活动时接受 CAR T 输注,但一些临床变量的影响,如对 CAR T 前化疗的反应性对 CAR T 的反应性的影响尚不清楚。在这项单中心研究中,我们研究了几种 CAR T 前变量对 CAR T 后结果的影响。60 例患者接受 axicabtagene-ciloleucel(axi-cel)的单采,其中 42 例(70.0%)为原发性难治性疾病。在单采和淋巴细胞耗竭之间进行桥接治疗的有 34 例(56.7%)。axi-cel 后,总缓解率为 63.3%。对即刻 CAR T 前治疗的反应性与 axi-cel、无进展生存期(PFS)或总生存期(OS)的反应无显著相关性。多变量分析确定,淋巴细胞耗竭前的大肿块疾病与较差的结局独立相关,而对即刻 CAR T 前治疗无反应的高负担疾病患者结局不佳。这些数据支持在 CAR T 候选者中进行治疗,无论他们对即刻 CAR T 前治疗的反应如何。对于有不良预后已知风险因素(大肿块疾病、高 LDH)的患者,应考虑进行临时治疗干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbcd/9753434/c54fad879a54/JCMM-26-5976-g001.jpg

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