https://orcid.org/0000-0002-0221-1835
Key Points
External validation confirmed the predictive value of the HT score for severe neutropenia, including early and late severe ICAHT
The HT score identified patients at risk of reduced survival and harbors potential to support risk stratification for severe infections
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.
