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在绝对淋巴细胞扩增时给予预防性地塞米松并不能降低免疫效应细胞相关迟发性神经毒性的风险或无事件生存期

英文原题:Prophylactic dexamethasone at the time of absolute lymphocyte expansion does not mitigate risk or event-free survival for immune effector cell associated delayed neurotoxicity.

查看英文原题

Prophylactic dexamethasone at the time of absolute lymphocyte expansion does not mitigate risk or event-free survival for immune effector cell associated delayed neurotoxicity.

PubMed 2026/08/10(内容时间) Blood Cancer J Q1 · IF 13.8(JCR 2025)

研究概要

2024年12月至2025年8月期间,我们在57例高ALC患者中评估了一种使用短程地塞米松(DEX)的预防策略,高ALC定义为CAR-T输注后连续监测中输注后ALC达到3 10 /L。

中文摘要

接受 ciltacabtagene autoleucel(cilta-cel)治疗后,较高的输注后绝对淋巴细胞计数(ALC)与免疫效应细胞相关迟发性神经毒性(IEC-DNT)风险增加相关,包括帕金森综合征(IEC-PKS)和颅神经麻痹(IEC-NP)。在 2024 年 12 月至 2025 年 8 月期间,我们在 57 例高 ALC 患者中评估了一种使用短疗程 dexamethasone(DEX)的预防策略;高 ALC 定义为 CAR-T 输注后连续监测中输注后 ALC 为 3 × 10⁹/L。DEX 以 10 mg 每日两次给药,至少三天。结局与 2022 年 2 月至 2024 年 11 月期间治疗的 104 例高 ALC 患者组成的历史对照队列进行比较。虽然 DEX 似乎减轻了面神经麻痹的严重程度,但并未显著改善 IEC-DNT、IEC-PKS 或 IEC-NP 的无事件生存期,也未降低 IEC-PKS 的严重程度。ALC 动力学分析显示,淋巴细胞扩增未出现统计学或生物学上有意义的降低,提示 dexamethasone 的剂量和持续时间可能不足,或额外的免疫和宿主因素促成 IEC-DNT 风险。这些发现凸显了皮质类固醇预防的作用有限,并强调需要更具机制针对性的策略,以减轻靶向 BCMA 的 CAR-T 治疗的这一具有挑战性的并发症。

展开英文摘要原文

High post-infusion absolute lymphocyte count (ALC) following ciltacabtagene autoleucel (cilta-cel) therapy is associated with an increased risk of immune effector cell-associated delayed neurotoxicity (IEC-DNT), including parkinsonism (IEC-PKS) and cranial nerve palsies (IEC-NP). Between December 2024 and August 2025, we evaluated a prophylactic strategy using a short course of dexamethasone (DEX) in 57 patients with high-ALC, defined as a post-infusion ALC of 3 10 /L on serial monitoring after CAR-T infusion. DEX was administered at 10 mg twice daily for a minimum of three days. Outcomes were compared with a historical control cohort of 104 patients with high-ALC treated between February 2022 and November 2024. While DEX appeared to attenuate the severity of facial nerve palsy, it did not significantly improve event-free survival for IEC-DNT, IEC-PKS, or IEC-NP, nor did it reduce the severity of IEC-PKS. Analysis of ALC kinetics demonstrated no statistically or biologically meaningful reduction in lymphocyte expansion, suggesting that the dose and duration of dexamethasone may be insufficient, or that additional immune and host factors contribute to the risk of IEC-DNT. These findings highlight the limited role of corticosteroid prophylaxis and underscore the need for more mechanistically targeted strategies to mitigate this challenging complication of BCMA-directed CAR-T therapy.

论文信息

作者
Lim KJ、Tan M、Parrondo R、Chhabra S、Schaefers C、Dooley K、De Menezes Silva Corraes A、Gupta M
第一作者单位
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.United States
通讯作者单位
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA. lin.yi@mayo.edu.United States
期刊
Blood cancer journal2026 Aug 10
原文标识
PubMed 42728267 · DOI 10.1038/s41408-026-01598-5