Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, MD, USA; George Washington University School of Medicine, Washington, DC, USA.
Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, MD, USA; Division of Biology and Biomedical Sciences, Washington University, St. Louis, MO, USA.
Mol Ther. 2024 Sep 4;32(9):2979-2983. doi: 10.1016/j.ymthe.2024.03.030. Epub 2024 Mar 26.
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.
随着嵌合抗原受体 (CAR) T 细胞疗法的扩展和更广泛地使用抗细胞因子导向疗法来减轻毒性,常规评估细胞因子可能有助于更好地了解毒性特征,指导治疗干预,并促进临床试验之间的比较。由于特定细胞因子的升高与 CAR T 细胞毒性、缓解策略以及反应相关,我们探讨了细胞因子检测方法的报告情况,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神经毒性综合征 (ICANS) 之间的相关性在临床试验中。在这项分析中,我们回顾了 21 项临床试验,涉及 60 篇论文,其中包括经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。我们强调了在 CAR T 细胞临床试验中细胞因子测量平台和面板的使用存在很大的差异和有限的报告。具体来说,在 60 篇出版物中,有 28 篇(46.7%)没有报告任何细胞因子数据,占 21 项临床试验中的 6 项(28.6%)。在报告细胞因子数据的 15 项试验中,至少使用了 4 种不同的平台。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,我们的论文支持需要建立细胞因子测量的标准化,作为改善 CAR T 细胞治疗结果的关键生物标志物的必要性。
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