CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Predictors of response to axicabtagene-ciloleucel CAR T cells in aggressive B cell lymphomas: A real-world study.
Predictors of response to axicabtagene-ciloleucel CAR T cells in aggressive B cell lymphomas: A real-world study.
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CAR-T 细胞疗法在复发/难治性弥漫性大B细胞淋巴瘤(DLBCL)中显示出有希望的疗效。虽然大多数患者在接受CAR-T 输注时存在活动性疾病,但一些临床变量(如对CAR-T 前化疗的反应性)对CAR-T 反应的影响尚不清楚。在这项单机构研究中,我们研究了几项CAR-T 前变量对CAR-T 后结局的影响。60名患者接受了axicabtagene-ciloleucel(axi-cel)的白细胞分离术,其中42名(70.0%)患有原发性难治性疾病。34名患者(56.7%)在白细胞分离术和淋巴细胞清除术之间接受了桥接治疗。axi-cel后,总缓解率为63.3%。对紧接CAR-T 前治疗的反应性与axi-cel的反应、无进展生存期(PFS)或总生存期(OS)无显著关联。多变量分析确定,淋巴细胞清除术前的巨块型疾病与较差结局独立相关,而表现为高肿瘤负荷疾病且对紧接CAR-T 前治疗无反应的患者结局极差。这些数据支持无论CAR-T 候选者对紧接CAR-T 前治疗的反应如何,都应继续进行该治疗。对于已知具有不良结局风险因素(巨块型疾病、高LDH)的患者,应考虑 interim 治疗干预。
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).
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