CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
BCMA CAR-T 治疗后的非 ICANS 神经毒性：4630 例多发性骨髓瘤患者的系统综述与荟萃分析
英文原题：Non-ICANS neurologic toxicity after BCMA CAR-T therapy: a systematic review and meta-analysis of 4630 patients with multiple myeloma.
查看英文原题
Non-ICANS neurologic toxicity after BCMA CAR-T therapy: a systematic review and meta-analysis of 4630 patients with multiple myeloma.
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中文摘要
B 细胞成熟抗原 (BCMA) 导向的CAR-T 细胞 疗法极大地改善了复发性或难治性多发性骨髓瘤患者的预后。尽管 CAR-T 相关细胞因子释放综合征和免疫效应细胞相关神经毒性综合征 (ICANS) 已得到充分表征，但非 ICANS 神经毒性 (NINT) 的定义仍然不明确，有关发病率和危险因素的数据有限。
我们遵循 PRISMA（系统评价和荟萃分析的首选报告项目）指南，对报告 BCMA 导向的 CAR-T 治疗后神经系统毒性的前瞻性临床试验和真实世界研究进行了系统评价和荟萃分析。使用随机效应荟萃分析来计算 NINT 的汇总点估计。进行荟萃回归来评估与治疗相关的风险预测因子。当有足够的详细信息时，报告的 NINT 按临床表型进行分类。纳入 55 个队列，共 4630 名接受治疗的患者。NINT 的汇总点估计值为 0.81%（95% 置信区间，0.37%-1.77%）。不同产品的发生率存在显着差异，ciltacabtagene autoleucel (cilta-cel) 后的 NINT 频率显着高于 idecabtagene vicleucel（ide-cel；4.6% vs 0.5%；P = .001）和实验性 BCMA 导向构建体（4.6% vs 0.3%；P = .02）。
此外，荟萃回归发现，与 ide-cel 相比，cilta-cel 与 NINT 风险增加独立相关。颅神经麻痹是最常报告的表型（32.3%，43 起事件），其次是运动和神经认知治疗引起的不良事件（12%，16 起事件），然后是周围神经病变（7.5%，10 起事件）。这项荟萃分析表明，NINT 是 BCMA 导向的 CAR-T 疗法（尤其是 cilta-cel）后的一种罕见但重要的毒性。需要标准化定义和改进 NINT 报告，以更好地描述风险并为监测策略提供信息。
展开英文摘要原文
B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapies have drastically improved outcomes for patients with relapsed or refractory multiple myeloma. Although CAR-T-associated cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) are well characterized, non-ICANS neurologic toxicities (NINTs) remain poorly defined, with limited data regarding incidence and risk factors.
We performed a systematic review and meta-analysis of prospective clinical trials and real-world studies reporting neurologic toxicities after BCMA-directed CAR-T therapy, following PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Random-effects meta-analysis was used to calculate a pooled point estimate of NINTs. Meta-regression was conducted to evaluate treatment-related predictors of risk.
Reported NINTs were categorized by clinical phenotype when sufficient detail was available. Fifty-five cohorts comprising 4630 treated patients were included. The pooled point estimate for NINTs was 0. 81% (95% confidence interval, 0. 37%-1. 77%). Incidence differed significantly by product, with a significantly higher frequency of NINTs after ciltacabtagene autoleucel (cilta-cel) than idecabtagene vicleucel (ide-cel; 4. 6% vs 0. 5%; P = . 001) and experimental BCMA-directed constructs (4. 6% vs 0. 3%; P = . 02).
Additionally, meta-regression identified cilta-cel as independently associated with increased NINT risk compared with ide-cel. Cranial nerve palsies were the most frequently reported phenotype (32. 3%, 43 events), followed by movement and neurocognitive treatment-emergent adverse events (12%, 16 events), then peripheral neuropathies (7.
5%, 10 events). This meta-analysis establishes that NINTs are a rare but important toxicity after BCMA-directed CAR-T therapy, particularly cilta-cel. Standardized definitions and improved reporting of NINTs are needed to better characterize risk and inform surveillance strategies.
论文信息
- 作者
- van Besien H、Ozkan G、Easton N、Tix T、Alhomoud M、Shouval R、Rejeski K、Yamshon S
- 单位
- Department of Medicine, Weill Cornell Medical College, New York, NY.United States
- 文献类型
- 系统综述 · 荟萃分析
- 期刊
- Blood advances2026 Aug 11
- 原文标识
- PubMed 41886632 · DOI 10.1182/bloodadvances.2026019617
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