With expansion of chimeric antigen receptor (CAR) T cell therapy and broader utilization of anti-cytokine directed therapeutics for toxicity mitigation, the routine assessment of cytokines may enhance understanding of toxicity profiles, guide therapeutic interventions, and facilitate cross-trial comparisons. As specific cytokine elevations can correlate with and provide insights into CAR T cell toxicity, mitigation strategies, and response, we explored the reporting of cytokine detection methods and assessed for the correlation of cytokines to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) across clinical trials. In this analysis, we reviewed 21 clinical trials across 60 manuscripts that featured a US Food and Drug Administration-approved CAR T cell construct or one of its predecessors. We highlight substantial variability and limited reporting of cytokine measurement platforms and panels used across CAR T cell clinical trials. Specifically, across 60 publications, 28 (46.7%) did not report any cytokine data, representing 6 of 21 (28.6%) clinical trials. In the 15 trials reporting cytokine data, at least 4 different platforms were used. Furthermore, correlation of cytokines with ICANS, CRS, and CRS severity was limited. Considering the fundamental role of cytokines in CAR T cell toxicity, our manuscript supports the need to establish standardization of cytokine measurements as a key biomarker essential to improving outcomes of CAR T cell therapy.

中文翻译：

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CAR T 细胞疗法中细胞因子分析的标准化需求

随着嵌合抗原受体（CAR）T细胞疗法的扩展和更广泛地利用抗细胞因子定向疗法来减轻毒性，细胞因子的常规评估可以增强对毒性特征的理解，指导治疗干预，并促进交叉试验比较。由于特定的细胞因子升高可以与 CAR T 细胞毒性、缓解策略和反应相关并提供见解，因此我们探索了细胞因子检测方法的报告，并评估了细胞因子与细胞因子释放综合征 (CRS) 和免疫效应细胞相关的相关性。跨临床试验的神经毒性综合征（ICANS）。在这项分析中，我们审查了 60 份手稿中的 21 项临床试验，这些试验采用了美国食品和药物管理局批准的 CAR T 细胞构建体或其前身之一。我们强调 CAR T 细胞临床试验中使用的细胞因子测量平台和面板的巨大差异和有限的报告。具体而言，在 60 篇出版物中，28 篇 (46.7%) 没有报告任何细胞因子数据，占 21 篇临床试验中的 6 篇 (28.6%)。在报告细胞因子数据的 15 项试验中，至少使用了 4 个不同的平台。此外，细胞因子与 ICANS、CRS 和 CRS 严重程度的相关性有限。考虑到细胞因子在 CAR T 细胞毒性中的基本作用，我们的手稿支持建立细胞因子测量标准化的必要性，作为改善 CAR T 细胞治疗结果所必需的关键生物标志物。