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CAR-T 细胞治疗相关毒性的管理策略:来自希腊调查的结果

英文原题:Management strategies for CAR-T cell therapy-related toxicities: results from a survey in Greece.

查看英文原题

Management strategies for CAR-T cell therapy-related toxicities: results from a survey in Greece.

PubMed 2025/05/30(内容时间) Front Med (Lausanne) Q1 · IF 3.6(JCR 2025)

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中文摘要

CAR-T 细胞疗法已改变了复发/难治性血液系统恶性肿瘤的治疗格局,提供了显著的缓解率。然而,包括细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)在内的严重毒性反应,正对患者管理构成挑战。这项多中心观察性研究评估了希腊六个移植中心在管理严重CRS和ICANS方面的预防和治疗策略。分析了173名接受CAR-T 细胞产品——axi-cel、tisa-cel和brexu-cel——的成年患者的数据。3级CRS的发生率在axi-cel中为6.6%,tisa-cel中为3.3%,brexu-cel接受者中为10%。4级CRS在axi-cel和brexu-cel接受者中记录为2.5%和5%,而5级CRS仅在brexu-cel中记录到(10%)。严重ICANS较少见,axi-cel的3级和4级发生率分别为7.5%和2.5%,而brexu-cel仅记录到3级(10%)。各中心采用了预防措施,包括左乙拉西坦和低剂量地塞米松,显著减少了严重毒性反应。托珠单抗用于CRS管理,在部分病例中辅以阿那白滞素或司妥昔单抗。早期干预策略有效减少了向严重毒性进展。

我们的发现强调了标准化预防和治疗方案在减轻CAR-T 相关毒性方面的重要性。毒性发生率的差异反映了患者人群、CAR-T 构建体和临床实践的差异。

进一步的研究对于优化个体化管理策略和推进CAR-T 疗法在临床环境中的安全性至关重要。

展开英文摘要原文

Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of relapsed or refractory hematologic malignancies, offering remarkable remission rates.

However, severe toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), are posing challenges to patient care. This multicenter observational study evaluated the prophylactic and treatment strategies for managing severe CRS and ICANS across six transplant centers in Greece. Data from 173 adult patients receiving CAR-T cell products-axi-cel, tisa-cel, and brexu-cel-were analyzed. The incidence of grade 3 CRS was 6. 6% for axi-cel, 3. 3% for tisa-cel, and 10% for brexu-cel recipients. Grade 4 CRS was documented in 2.

5% and 5% in axi-cel and brexu-cel recipients, while grade 5 CRS was recorder only in brexu-cel (10%). Severe ICANS was less frequent, with grade 3 and 4 rates of 7. 5% and 2. 5% for axi-cel, while brexu-cel documented only grade 3 (10%).

Centers utilized prophylactic measures, including levetiracetam and low-dose dexamethasone, significantly reducing severe toxicities. Tocilizumab was administered for CRS management, supplemented by anakinra or siltuximab in select cases. Early intervention strategies effectively minimized progression to severe toxicity.

Our findings underscore the importance of standardized prophylactic and therapeutic protocols in mitigating CAR-T-related toxicities. The variability in toxicity incidence reflects differences in patient populations, CAR-T constructs, and clinical practices.

Further research is essential to optimize individualized management strategies and advance the safety of CAR-T therapies in clinical settings.

论文信息

作者
Gavriilaki E、Tzannou I、Vardi A、Tsonis I、Liga M、Gkirkas K、Ximeri M、Bousiou Z
单位
Hematology Department-BMT Unit, George Papanikolaou General Hospital, Thessaloniki, Greece.Greece
期刊
Frontiers in medicine2025
原文标识
PubMed 40520784 · DOI 10.3389/fmed.2025.1553966