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CD19 CAR-T 细胞产品类型对复发/难治性侵袭性 B 细胞非霍奇金淋巴瘤结局的影响

英文原题：Impact of CD19 CAR T-cell product type on outcomes in relapsed or refractory aggressive B-NHL.

查看英文原题

Impact of CD19 CAR T-cell product type on outcomes in relapsed or refractory aggressive B-NHL.

PubMed 2022/06/30（内容时间） Blood Q1 · IF 23.9（JCR 2025）

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靶点：CD19技术：CAR-T非霍奇金淋巴瘤地区：美国
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中文摘要

CD19靶向嵌合抗原受体工程化（CD19 CAR）T细胞是新型疗法，对复发/难治性（R/R）侵袭性B细胞非霍奇金淋巴瘤（B-NHL）患者显示出巨大前景。单臂研究显示，不同CD19 CAR-T 细胞产品的结局存在显著差异。为评估CAR-T 细胞产品类型对结局的独立影响，我们回顾性分析了129例R/R侵袭性B-NHL患者的数据，这些患者接受环磷酰胺和氟达拉滨淋巴细胞清除后，接受市售CD19 CAR-T 细胞疗法（axicabtagene ciloleucel [axicel]或tisagenlecleucel [tisacel]），或接受研究性产品JCAR014的1/2期临床试验（NCT01865617）。在调整年龄、造血细胞移植特异性合并症指数、乳酸脱氢酶（LDH）、最大病灶直径和绝对淋巴细胞计数（ALC）后，CAR-T 细胞产品类型在多变量模型中仍与结局相关。

与axicel相比，JCAR014独立与较低的细胞因子释放综合征（CRS）严重程度相关（调整比值比[aOR]，0.19；95%置信区间[CI]，0.08-0.46），与axicel相比，tisacel有CRS严重程度较低的趋势（aOR，0.47；95% CI，0.21-1.06；P = .07）。与axicel相比，tisacel（aOR，0.17；95% CI，0.06-0.48）和JCAR014（aOR，0.17；95% CI，0.06-0.47）均与较低的免疫效应细胞相关神经毒性综合征严重程度相关。与axicel相比，tisacel和JCAR014预测的完全缓解（CR）几率较低。尽管使用基于正电子发射断层扫描或计算机断层扫描的缓解标准的敏感性分析也提示axicel优于JCAR014，但tisacel与axicel的影响变得不确定。较高的白细胞分离术前LDH、最大病灶直径和较低的ALC与较低的CR几率独立相关。

我们得出结论，CD19 CAR-T 细胞产品类型独立影响R/R侵袭性B-NHL患者的毒性和疗效。

展开英文摘要原文

CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells are novel therapies showing great promise for patients with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). Single-arm studies showed significant variations in outcomes across distinct CD19 CAR T-cell products. To estimate the independent impact of the CAR T-cell product type on outcomes, we retrospectively analyzed data from 129 patients with R/R aggressive B-NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by either a commercially available CD19 CAR T-cell therapy (axicabtagene ciloleucel [axicel] or tisagenlecleucel [tisacel]), or the investigational product JCAR014 on a phase 1/2 clinical trial (NCT01865617). After adjustment for age, hematopoietic cell transplantation-specific comorbidity index, lactate dehydrogenase (LDH), largest lesion diameter, and absolute lymphocyte count (ALC), CAR T-cell product type remained associated with outcomes in multivariable models.

JCAR014 was independently associated with lower cytokine release syndrome (CRS) severity compared with axicel (adjusted odds ratio [aOR], 0. 19; 95% confidence interval [CI]; 0. 08-0. 46), with a trend toward lower CRS severity with tisacel compared with axicel (aOR, 0. 47; 95% CI, 0. 21-1. 06; P = . 07). Tisacel (aOR, 0. 17; 95% CI, 0. 06-0. 48) and JCAR014 (aOR, 0. 17; 95% CI, 0. 06-0. 47) were both associated with lower immune effector cell-associated neurotoxicity syndrome severity compared with axicel.

Lower odds of complete response (CR) were predicted with tisacel and JCAR014 compared with axicel. Although sensitivity analyses using either positron emission tomography- or computed tomography-based response criteria also suggested higher efficacy of axicel over JCAR014, the impact of tisacel vs axicel became undetermined. Higher preleukapheresis LDH, largest lesion diameter, and lower ALC were independently associated with lower odds of CR.

We conclude that CD19 CAR T-cell product type independently impacts toxicity and efficacy in R/R aggressive B-NHL patients.

论文信息

作者
Gauthier J、Gazeau N、Hirayama AV、Hill JA、Wu V、Cearley A、Perkins P、Kirk A
第一作者单位
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.United States
通讯作者单位
Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health and Science University, Portland, OR.
期刊
Blood2022 Jun 30
原文标识
PubMed 35439295　·　DOI 10.1182/blood.2021014497

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