Barker Kenneth, Marco Tom, Husnain Muhammad, Katsanis Emmanuel
Department of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Department of Hematology and Oncology, University of Arizona Cancer Center, Tucson, AZ 85719, USA.
Cancers (Basel). 2025 Mar 7;17(6):918. doi: 10.3390/cancers17060918.
Cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) are both serious complications of CAR-T therapy associated with endothelial dysfunction, prompting prior use of a modified version of the endothelial activation and stress index (m-EASIX) to predict the occurrence of severe ICANS and CRS. Previous studies have linked both hypophosphatemia and elevated IL6 levels to CRS and ICANS. Our study aimed to enhance the early prediction of both syndromes by integrating phosphorous and IL-6 both together and separately into the m-EASIX score. Forty-two patients with non-Hodgkin's lymphoma presenting for CAR-T treatment were used to generate three variations in the m-EASIX score, assessing performance for the clinically actionable time points of day +0 through day +3. The addition of phosphorous through the P-m-EASIX improved the predictive capabilities for the occurrence of ICANS, most notably on day +1 (AUC 89.6%; = 0.0090, OR of 2.23; = 0.0096) compared to the m-EASIX (AUC 80.8%; = 0.0047, OR 1.72; = 0.0046). The P-m-EASIX also showed enhanced predictive capabilities for the occurrence of CRS, with peak discriminatory function on day +3 (AUC 92.0%; = <0.0001, OR 2.21; = 0.0014). The addition of IL6 in the IL6-m-EASIX showed the highest discriminatory capacity for the prediction of CRS progression to grade ≥ 2 with peak function on day +3 (AUC 89.7%; = 0.0040, OR 1.57; = 0.031). Incorporating phosphorus levels into the m-EASIX score offered a cost-effective and straightforward method to improve the prediction of CAR-T toxicities. Larger-scale studies assessing the effectiveness of including phosphorus and IL-6 in the m-EASIX score to mitigate complications associated with CAR-T therapy are warranted.
细胞因子释放综合征（CRS）和免疫细胞相关神经毒性综合征（ICANS）都是嵌合抗原受体T细胞（CAR-T）疗法的严重并发症，与内皮功能障碍相关，这促使之前使用改良版的内皮激活和应激指数（m-EASIX）来预测严重ICANS和CRS的发生。先前的研究已将低磷血症和白细胞介素6（IL6）水平升高与CRS和ICANS联系起来。我们的研究旨在通过将磷和IL-6分别及共同纳入m-EASIX评分来加强对这两种综合征的早期预测。42例接受CAR-T治疗的非霍奇金淋巴瘤患者被用于生成m-EASIX评分的三种变体，评估从第0天到第3天临床可采取行动时间点的预测性能。通过磷改良的m-EASIX（P-m-EASIX）加入磷后提高了对ICANS发生的预测能力，与m-EASIX相比，在第1天最为显著（曲线下面积[AUC] 89.6%；P = 0.0090，比值比[OR] 2.23；P = 0.0096）（m-EASIX的AUC为80.8%；P = 0.0047，OR 1.72；P = 0.0046）。P-m-EASIX对CRS的发生也显示出增强的预测能力，在第3天具有最高的鉴别功能（AUC 92.0%；P = <0.0001，OR 2.21；P = 0.0014）。在IL6改良的m-EASIX（IL6-m-EASIX）中加入IL6对预测CRS进展至≥2级显示出最高的鉴别能力，在第3天具有峰值功能（AUC 89.7%；P = 0.0040，OR 1.57；P = 0.031）。将磷水平纳入m-EASIX评分提供了一种经济有效且简单的方法来改善对CAR-T毒性的预测。有必要开展更大规模的研究来评估在m-EASIX评分中纳入磷和IL-6以减轻与CAR-T疗法相关并发症的有效性。
