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在输注时无可测量疾病的复发/难治性弥漫性大 B 细胞淋巴瘤患者中使用 tisagenlecleucel。

Tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma patients without measurable disease at infusion.

机构信息

Hematopoietic Cellular Therapy Program, The University of Chicago Medicine, Chicago, IL.

Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, OR.

出版信息

Blood Adv. 2019 Jul 23;3(14):2230-2236. doi: 10.1182/bloodadvances.2019000151.

Abstract

Tisagenlecleucel demonstrated high rates of durable responses in adult patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. Most patients (92%) received bridging therapies to control disease after study entry and before tisagenlecleucel infusion. Here, we examine the efficacy and safety of tisagenlecleucel in the subset of 7 patients who achieved complete response (CR) after bridging therapy and before tisagenlecleucel infusion. Tisagenlecleucel rapidly expanded in all 7 patients, and the transgene levels were measurable for up to 2 years after infusion. After infusion, all 7 patients were still in CR at the month 3 evaluation, and 5 of 7 patients remained progression-free >12 months. Adverse events were similar to the overall JULIET population. Cytokine release syndrome (CRS) was reported in 4 of 7 patients (grade 2 = 2 and grade 3 = 2 using the Penn grading scale), and 1 patient experienced grade 1 neurotoxicity. No patient required tocilizumab or steroids for CRS management. These data provide preliminary evidence of tisagenlecleucel efficacy in patients with r/r DLBCL without detectable disease after bridging or salvage therapies and warrant further investigation of tisagenlecleucel as consolidative therapy in future trials. This trial was registered at www.clinicaltrials.gov as #NCT02445248.

摘要

在 JULIET 试验中,Tisagenlecleucel 在复发或难治性弥漫性大 B 细胞淋巴瘤(r/r DLBCL)的成年患者中显示出高比例的持久缓解率。大多数患者(92%)在研究入组后和Tisagenlecleucel 输注前接受了桥接治疗来控制疾病。在这里,我们研究了Tisagenlecleucel 在 7 名患者亚组中的疗效和安全性,这些患者在桥接治疗后和Tisagenlecleucel 输注前达到完全缓解(CR)。Tisagenlecleucel 在所有 7 名患者中均迅速扩增,输注后长达 2 年仍可检测到转基因水平。输注后,所有 7 名患者在第 3 个月评估时仍处于 CR,7 名患者中有 5 名无进展生存期>12 个月。不良事件与总体 JULIET 人群相似。4 名患者(根据 Penn 分级标准,2 级=2,3 级=2)报告了细胞因子释放综合征(CRS),1 名患者出现 1 级神经毒性。没有患者因 CRS 管理需要使用托珠单抗或类固醇。这些数据提供了Tisagenlecleucel 在桥接或挽救治疗后无可检测疾病的 r/r DLBCL 患者中的初步疗效证据,并需要进一步研究Tisagenlecleucel 作为未来试验中的巩固治疗。该试验在 www.clinicaltrials.gov 上注册,编号为 #NCT02445248。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98b4/6650727/e784a4569b58/advancesADV2019000151absf1.jpg

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