基于人群的 EASIX 评分外部验证以预测 CAR-T 细胞相关毒性

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can hamper the clinical benefit of CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). To assess the risk of CRS and ICANS, the endothelial activation and stress index (EASIX), the modified EASIX (m-EASIX), simplified EASIX (s-EASIX), and EASIX with CRP/ferritin (EASIX-F(C)) were proposed.

This study validates these scores in a consecutive population-based cohort. Patients with r/r LBCL treated with axicabtagene ciloleucel were included ( n = 154). EASIX scores were calculated at baseline, before lymphodepletion (pre-LD) and at CAR T-cell infusion. The EASIX and the s-EASIX at pre-LD were significantly associated with ICANS grade 2 (both p = 0. 04), and the EASIX approached statistical significance at infusion ( p = 0. 05).

However, the predictive performance was moderate, with area under the curves of 0. 61-0. 62. Validation of the EASIX-FC revealed that patients in the intermediate risk group had an increased risk of ICANS grade 2 compared to low-risk patients. No significant associations between EASIX scores and CRS/ICANS grade 3 were found. The (m-/s-) EASIX can be used to assess the risk of ICANS grade 2 in patients treated with CAR T-cell therapy.

However, due to the moderate performance of the scores, further optimization needs to be performed before broad implementation as a clinical tool, directing early intervention and guiding outpatient CAR T-cell treatment.