Addition of Phosphorous and IL6 to m-EASIX Score Improves Detection of ICANS and CRS, as Well as CRS Progression

Introduction: 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. Methods: 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. Results: 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%; p = 0.0090, OR of 2.23; p = 0.0096) compared to the m-EASIX (AUC 80.8%; p = 0.0047, OR 1.72; p = 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%; p = <0.0001, OR 2.21; p = 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%; p = 0.0040, OR 1.57; p = 0.031). Conclusions: 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.