Cellular kinetics of CTL019 in relapsed/refractory B-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia
Cellular kinetics of CTL019 in relapsed/refractory B-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia
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DOI：
10.1182/blood-2017-06-786129
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发表时间：
2017-11-23
期刊：
影响因子：
20.3
通讯作者：
Lacey, Simon F.
中科院分区：
文献类型：
--
作者：
Mueller, Karen Thudium;Maude, Shannon L.;Lacey, Simon F.
Tisagenlecleucel（CTL 019）是一种研究性免疫疗法，涉及用编码嵌合抗原受体的转基因对患者自身的T细胞进行重编程，以识别和消除表达CD 19的细胞。我们之前报道了CTL 019在复发/难治性B细胞急性淋巴细胞白血病（ALL）和慢性淋巴细胞白血病（CLL）患者中取得了令人印象深刻的临床疗效，包括CTL 019细胞的扩增和持久性，这与对治疗的反应相关。在这里，我们在2种不同疾病（ALL和CLL）中用CTL 019治疗的103名患者的较大队列中进行了CTL 019的正式细胞动力学分析。使用定量聚合酶链反应和流式细胞术测量外周血和骨髓中的CTL 019。外周血中的CTL 019水平通常在输注后10至14天达到峰值，然后随时间缓慢下降。完全缓解（CR）/CR伴计数不完全恢复的患者外周血中的CTL 019水平高于无应答患者（P
Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. We previously reported that CTL019 achieved impressive clinical efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), including the expansion and persistence of CTL019 cells, which correlates with response to therapy. Here, we performed formal cellular kinetic analyses of CTL019 in a larger cohort of 103 patients treated with CTL019 in 2 different diseases (ALL and CLL). CTL019 was measured in peripheral blood and bone marrow, using quantitative polymerase chain reaction and flow cytometry. CTL019 levels in peripheral blood typically peaked at 10 to 14 days postinfusion and then declined slowly over time. Patients with complete response (CR)/CRwith incomplete count recovery had higher levels of CTL019 in peripheral blood, with greater maximal concentration and area under the curve values compared with non-responding patients (P