Assessing the Predictive Value of Pre-Lymphodepletion and Infusion Endothelial Activation and Stress Index in CD19-Directed CAR-T Therapy for B-Cell Lymphoma

Introduction The Endothelial Activation and Stress Index (EASIX) formula (creatinine [mg/dL] × lactate dehydrogenase [U/L])/platelets [109 cells/L]) measures endothelial activation and is relevant in CAR T-related toxicities. Prior studies linked pre-lymphodepletion (pre-LD) EASIX and ferritin (EASIX-F) to CRS grade 2-4 and EASIX combined with ferritin and CRP (EASIX-FC) to ICANS grade 2-4 in lymphoma patients (pts) treated with Axi-cel. We aimed to assess their predictive value at pre-LD and CAR-T infusion in B cell lymphoma pts receiving CD19-directed CAR T therapy. Method We retrospectively studied 97 pts with B cell lymphoma who received CD19 CAR T from Dec 2018 to Mar 2023. EASIX-F and EASIX-FC at pre-LD and infusion were calculated per original publication (PMID: 34264268). We estimated the cumulative incidence of CRS and ICANS starting from the infusion date, considering death before toxicity as a competing risk. Univariate Cox-regression was conducted using SPSS v.29. Result Baseline patient characteristics in Table 1. CRS occurred in 88% (30% grade 2-4), while ICANS was recorded in 44% (24% grade 2-4). Pre-LD and infusion EASIX-F and EASIX-FC were calculable in 97-99% of pts. Pre-LD EASIX-F predicted CRS grade 2-4: 20% in low (reference(ref)), 41% (Hazard ratio (HR) 2.2; 95% Confidence interval (CI) 1.04-5; p=.03) in intermediate, and 75% (HR 4.36; 95% CI 1.2-15.4; p=.02) in high risk. Infusion EASIX-F showed no correlation with CRS grade 2-4 (p=.6) (Fig 1). EASIX-FC was not associated with ICANS grade 2-4 at pre-LD or infusion. Cumulative incidence of ICANS grade 2-4 was 26%, 17%, and 40% at pre-LD and 30%, 19%, 25% at infusion, in low, intermediate, high risk, respectively. Findings differ from prior studies, possibly due to limited sample size and lower severe ICANS rate. Response data were available for 93% of pts. No significant difference in 30-day complete response (CR) was observed according to EASIX-F and EASIX-FC at various time points. However, high risk pts had a significantly lower overall response rate (≥PR) compared to intermediate and low risk. This difference was statistically significant in pre-LD EASIX-F (p=.02), infusion EASIX-F (p=.003), and infusion EASIX-FC (p=.002). Median follow-up: 8 months (mon) (range, 5-49). We observed a significant association between infusion EASIX-F and PFS (p=.003). In the high risk, median PFS was 2.8 mon (HR 3.05; 95% CI 1.16-8.04; p=.024), while in intermediate, was not reached (HR 0.69; 95% CI 0.34-1.3; p=.2), and was 7.7 mon in low risk (ref) (Fig 2). While pre-LD EASIX-F and EASIX-FC lacked significant associations, a trend towards worse PFS in high risk pts emerged. Conclusion These data highlight EASIX's predictive value for both toxicity and treatment response in CD19 CAR T-treated B cell lymphoma pts. The score may guide toxicity management and help to identify suitable CAR T candidates. Further, larger studies are warranted.