Non-ICANS neurologic toxicity after BCMA CAR-T therapy: a systematic review and meta-analysis of 4630 patients with 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 incidenceand risk factors.

尽管CAR-T相关的细胞因子释放综合征和免疫效应细胞相关的神经毒性综合征(ICANS)已被充分描述，但非ICANS神经毒性(NINTs)仍定义不清，关于其发生率和风险因素的数据有限。

We performed a systematic reviewand meta-analysisof 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.

我们根据PRISMA（系统评价和荟萃分析首选报告项目）指南，对报道了BCMA导向CAR-T疗法后神经系统毒性发生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。

Random-effects meta-analysiswas used to calculate a pooled point estimate of NINTs.

使用随机效应荟萃分析计算了NINTs的汇总点估计值。

Meta-regression was conducted to evaluate treatment-related predictors of risk.

进行了元回归分析，以评估与治疗相关的风险预测因素。

Reported NINTs were categorized by clinical phenotype when sufficient detail was available.

当有足够的详细信息时，报告的NINTs根据临床表型进行分类。

Fifty-five cohorts comprising 4630 treated patients were included.

共纳入了55个队列，包含4630名接受治疗的患者。

The pooled point estimate for NINTs was 0.81% (95% confidence interval, 0.37%-1.77%).

NINTs的汇总点估计值为0.81%（95%置信区间，0.37%-1.77%）。

Incidencediffered 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).

发生率因产品而异，与idecabtagene vicleucel（ide-cel；4.6% vs 0.5%；P = .001）和实验性BCMA导向构造物（4.6% vs 0.3%；P = .02）相比，接受ciltacabtagene autoleucel（cilta-cel）治疗后NINTs的发生频率显著更高。

Additionally, meta-regression identified cilta-cel as independently associated with increased NINT risk compared with ide-cel.

此外，元回归分析确定cilta-cel与ide-cel相比，独立地与NINT风险增加相关。

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).

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相关的不良事件（12%，16起事件），然后是周围神经病变（7.5%，10起事件）。

This meta-analysisestablishes that NINTs are a rare but important toxicity after BCMA-directed CAR-T therapy, particularly cilta-cel.

这项荟萃分析确定，NINTs是在BCMA导向的CAR-T疗法后一种罕见但重要的毒性，特别是对于cilta-cel。

Standardized definitions and improved reporting of NINTs are needed to better characterize risk and inform surveillance strategies.

需要标准化定义并改进非侵袭性肿瘤（NINTs）的报告，以更好地描述风险并指导监测策略。