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复发/难治性非霍奇金淋巴瘤患者接受博纳吐单抗治疗时T细胞和B细胞动力学与临床反应的关系

Relationship of T- and B-cell kinetics to clinical response in patients with relapsed/refractory non-Hodgkin lymphoma treated with blinatumomab.

作者信息

Nägele Virginie, Zugmaier Gerhard, Goebeler Maria-Elisabeth, Viardot Andreas, Bargou Ralf, Kufer Peter, Klinger Matthias

机构信息

Amgen Research (Munich) GmbH, Munich, Germany.

Amgen Research (Munich) GmbH, Munich, Germany.

出版信息

Exp Hematol. 2021 Aug;100:32-36. doi: 10.1016/j.exphem.2021.06.005. Epub 2021 Jul 3.

Abstract

Blinatumomab is a first-in-class immunotherapy based on the bispecific T-cell engager (BiTE®) immune-oncology platform, which redirects CD3 T cells to kill CD19 target cells. The objective of this analysis was to describe the correlation between B- and T-cell kinetics and response to blinatumomab in patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL). The clinical efficacy of treatment with blinatumomab in patients with r/r NHL was recently investigated in a phase 1 dose-escalation and expansion trial (NCT00274742) wherein 76 patients received blinatumomab by continuous intravenous infusion at various doses (0.5-90 μg/m/day). B-Cell depletion and expansion of CD3, CD4, and CD8 T cells was analyzed in patients stratified per clinical response (complete response [CR], n = 16; partial response [PR], stable disease [SD], or progressive disease [PD], n = 54) for at least 4 weeks (additional 4 weeks after clinical benefit) from the date of administration of blinatumomab until dose-limiting toxicity or PD. B-cell depletion kinetics were faster in patients who had a CR than in patients who did not have a complete response (PR, SD, or PD). T-cell expansion (T-cell counts exceeding the baseline level on day 22) was more pronounced in patients with CR than in patients without CR. T-cell expansion in patients with CR correlated with increased T-cell counts of both CD4 and CD8 T cells compared with patients without CR. Patients with r/r NHL who achieved a CR had faster B-cell depletion and increased expansion of CD3, CD4, and CD8 T cells than patients who did not achieve a CR.

摘要

博纳吐单抗是一种基于双特异性T细胞衔接器(BiTE®)免疫肿瘤学平台的首创免疫疗法,该平台可使CD3 T细胞重新定向以杀死CD19靶细胞。本分析的目的是描述复发或难治性(r/r)非霍奇金淋巴瘤(NHL)患者的B细胞和T细胞动力学与对博纳吐单抗反应之间的相关性。最近在一项1期剂量递增和扩展试验(NCT00274742)中研究了博纳吐单抗治疗r/r NHL患者的临床疗效,其中76例患者接受了不同剂量(0.5-90μg/m²/天)的博纳吐单抗持续静脉输注。从博纳吐单抗给药之日起至出现剂量限制性毒性或疾病进展,对根据临床反应分层的患者(完全缓解[CR],n = 16;部分缓解[PR]、疾病稳定[SD]或疾病进展[PD],n = 54)进行至少4周(临床获益后再额外4周)的B细胞耗竭以及CD3、CD4和CD8 T细胞扩增分析。达到CR的患者的B细胞耗竭动力学比未达到完全缓解(PR、SD或PD)的患者更快。CR患者的T细胞扩增(第22天T细胞计数超过基线水平)比未达到CR的患者更明显。与未达到CR的患者相比,CR患者的T细胞扩增与CD4和CD8 T细胞的T细胞计数增加相关。与未达到CR的患者相比,达到CR的r/r NHL患者的B细胞耗竭更快,CD3、CD4和CD8 T细胞的扩增增加。

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