Population-based validation of the CAR-HEMATOTOX for hematotoxicity, infections and survival after CART in R/R LBCL

Abstract

Early identification of patients at risk for immune effector cell-associated hematotoxicity (ICAHT) is essential to minimize non-relapse mortality. The CAR-HEMATOTOX (HT) score is an implemented risk-stratification tool for ICAHT, infections and survival in relapsed/refractory large B-cell lymphoma (R/R LBCL) patients receiving CAR T-cell therapy (CART). Although validated in its defining study, the HT score was developed in a small cohort, necessitating independent external validation. This study externally validates the HT score in a real-world population-based cohort of adults with R/R LBCL receiving CART. The HT score, based on absolute neutrophil count, hemoglobin, platelets, C-reactive protein, and ferritin, was calculated before lymphodepleting chemotherapy. Of 245 consecutive patients, 171 (70%) had a HT score ≥2 (HThigh). The initial endpoint, clinically significant neutropenia (ANC < 500/µL for ≥14 days), occurred in 21% of patients. The binary HT score was associated with clinically significant neutropenia (OR 2.94 [95%CI 1.27-6.80]; P = 0.012) with a good predictive performance (AUC = 0.73). Similar results were achieved for early and late ICAHT ≥ grade 3 (OR 2.92, [95% CI 1.19 - 7.14]; P = 0.019; OR 2.42 [95% CI 1.31 - 4.47]; P = 0.005). A trend towards an association with severe infections was observed (OR 2.02 [95%CI 0.91-4.48], P = 0.085). HThigh patients had a lower progression-free and overall survival (HRs 1.84 [95%CI 1.15-2.93]; P = 0.011, and 2.83 [95%CI 1.64-4.87]; P < 0.001, respectively). The HT score identified CART-treated R/R LBCL patients at risk for clinically significant neutropenia, poor survival outcomes, and potentially severe infections.