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侵袭性 B 细胞淋巴瘤患者中 Axicabtagene Ciloleucel 治疗后复发的预测因素与管理

英文原题:Predictors and Management of Relapse to Axicabtagene Ciloleucel in Patients with Aggressive B-cell Lymphoma.

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Predictors and Management of Relapse to Axicabtagene Ciloleucel in Patients with Aggressive B-cell Lymphoma.

PubMed 2023/01/17(内容时间) Hematol Oncol Stem Cell Ther

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研究概要

CRS 分级和 ALC Leuk 与 axi-cel 治疗获得更好结局相关。

中文摘要

我们回顾性研究了2018至2020年间在Mayo Clinic两个中心接受axicabtagene ciloleucel(axi-cel)治疗的aNHL患者,评估预测因素、毒性及CAR-T 细胞治疗后挽救方案的疗效。

34例患者接受axi-cel治疗,中位住院时间为14天。91%的患者发生任意级别细胞因子释放综合征(CRS),41%的患者发生任意级别免疫效应细胞相关神经毒性综合征。另有71%的患者对治疗有应答,53%达到完全缓解(CR)。CRS分级与CR相关,白细胞单采时绝对淋巴细胞计数(ALC Leuk)与总生存期(OS)相关。中位随访6.8个月(四分位距[IQR]:4.6–14.9)后,15例患者(44%)出现疾病进展(PD)。多数患者(60%)在最初3个月内进展,且肿瘤持续表达CD19。基线C反应蛋白升高会增加PD风险;铁蛋白升高则增加PD和死亡风险。12例患者接受挽救治疗,但仅3例有应答。axi-cel治疗后复发/难治患者的中位OS为3个月(IQR:1.3–5.1)。

CRS分级和ALC Leuk与axi-cel治疗结局较好相关。此外,基线炎症标志物升高与PD及生存期缩短相关。axi-cel输注后数月内常发生复发,且预后较差;因此亟需为该患者人群开发新型有效治疗方案。

展开英文摘要原文

We performed a retrospective study of aNHL patients treated with axicabtagene ciloleucel (axi-cel) at two Mayo Clinic centers between 2018 and 2020. We evaluated predictive factors, toxicities, and responses to salvage regimens after CAR T-cell therapy.

Thirty-four patients received axi-cel with a median length of hospitalization of 14 days. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome of any grade occurred in 91% and 41% of patients, respectively. Furthermore, 71% of patients responded to therapy, with 53% achieving a complete response (CR). The CRS grade and absolute lymphocyte count at leukapheresis (ALC Leuk ) correlated with CR and overall survival (OS), respectively. After a median follow-up of 6.8 months (interquartile range [IQR] 4.6-14.9), 15 patients (44%) showed progressive disease (PD). Most patients (60%) progressed during the first 3 months and had persistent CD19 tumor expression. Elevated C-reactive protein at baseline increased the risk of PD, whereas elevated ferritin increased PD and mortality risk. Twelve patients received salvage therapy, but only three responded. Median OS of relapsed/refractory patients to axi-cel was 3 months (IQR 1.3-5.1).

The grade of CRS and ALC Leuk correlated with better outcomes to axi-cel therapy. In addition, elevated inflammatory markers at baseline were associated with PD and shorter survival. Relapses after treatment frequently occur within months after axi-cel infusion; they confer a poor prognosis and create an urgent need for novel and effective treatment options in this patient population.

论文信息

作者
Forero-Forero JV、Lengerke-Diaz PA、Moreno-Cortes E、Melody M、Rahman ZA、Rosenthal AC、Kharfan-Dabaja MA、Castro JE
单位
Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USA.United States
期刊
Hematology/oncology and stem cell therapy2023 Jan 17
原文标识
PubMed 34562407 · DOI 10.1016/j.hemonc.2021.09.001