Further modification of the EASIX score through the addition of phosphorous and IL-6 improves prediction of CRS and ICANS after CAR-T therapy

Abstract Cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) are severe complications of CAR-T therapy linked to endothelial dysfunction. The modified Endothelial Activation and Stress Index (m-EASIX) score predicts severe ICANS and CRS. Both hypophosphatemia and elevated IL-6 are associated with these syndromes. Our study aimed to improve early prediction by incorporating phosphorus and IL-6 into the m-EASIX score. Forty-two patients with non-Hodgkin’s lymphoma receiving CAR-T treatment were used to generate three m-EASIX score variations, assessing performance from the clinically actionable timepoints of day + 0 to day + 3. The P-m-EASIX, which includes phosphorus, enhanced prediction for ICANS on day + 1 (AUC 89.6%; P = 0.0090, OR 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 improved prediction for CRS on day + 3 (AUC 92.0%; P < 0.0001, OR 2.21; P = 0.0014). Incorporating IL-6, (IL6-m-EASIX) showed the highest capacity for predicting CRS progression to grade ≥ 2 on day + 3 (AUC 89.7%; P = 0.0040, OR 1.57; P = 0.031). Larger studies are needed to evaluate the effectiveness of including phosphorus and IL-6 in the m-EASIX score to reduce CAR-T therapy complications.