Addition of IL-6 and phosphate to the m-EASIX score and detection of ICANS and CRS progression.

Abstract

e14511 Background: Cytokine release syndrome (CRS) and immune cell associated neurotoxicity syndrome (ICANS) can be severe complications of CAR-T infusion. Both syndromes have been associated with endothelial dysfunction which prompted prior use of a modified version of the Endothelial Activation and Stress Index (m-EASIX) to predict the occurrence of severe grades of ICANS and CRS. Recent studies have linked low phosphorous (P) levels to both syndromes, and IL-6 is a known mediator of both. Our study aimed to enhance early prediction of CRS and ICANS by integrating both P and IL-6 into the m-EASIX score. Methods: This retrospective study included 44 patients (26 male and 18 female) ranging from 42 to 86 years old with non-Hodgkin's lymphoma presenting to the University of Arizona Cancer Center for CAR-T treatment. P, CRP, IL-6, and LDH were recorded up to 7 days before and 14 days after CAR-T infusion. All platelet levels were recorded the day of infusion. Variations of the m-EASIX score as outlined in table 1 were then calculated. The values of P were cubed to ensure relative differences in P had proportional consistency to differences in other values. The scores were then used to generate ROC curves for the occurrence of CRS, ICANS, and the progression of CRS to grade ≥2 with CI generated through the Wilson/Brown method. Results: Of the 44 patients, 21 developed CRS alone, 12 developed ICANS+CRS, and 11 developed neither. 18 patients had progression of CRS to grade ≥2. The median day of onset for CRS, ICANS, and progression of CRS to grade ≥2 was 2, 5, and 4 days respectively. Day 3 post infusion yielded the highest values of area under the curve (AUC) with each variation of the m-EASIX score statistically significant with a p<0.001 as represented in table 1. The addition of P and IL-6 to the m-EASIX score increased AUC, sensitivity, and specificity for the occurrence of CRS, ICANS, and progression of CRS to grade ≥2. Conclusions: The inclusion of P and IL-6 in the m-EASIX score improved the sensitivity and specificity of detecting CRS, CRS progression, and the development of ICANS on the 3rd day post infusion. Larger scale studies investigating the efficacy of inclusion of P and IL-6 in the m-EASIX score in guiding early interventions to mitigate complications associated with CAR-T therapy are necessary. [Table: see text]