基于人群的验证：CAR-HEMATOTOX 对 R/R LBCL 患者 CAR-T 后血液学毒性、感染和生存的预测价值

Early identification of patients at risk of immune effector cell-associated hematotoxicity (ICAHT) is essential to minimize nonrelapse mortality. The CAR-HEMATOTOX (HT) score is an implemented risk-stratification tool for ICAHT, infections, and survival in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL) receiving chimeric antigen receptor 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 (ANC), hemoglobin, platelets, C-reactive protein, and ferritin, was calculated before lymphodepleting chemotherapy. Of 245 consecutive patients, 171 (70%) had an HT score of ≥2 (HThigh). The initial end point, clinically significant neutropenia (ANC of <500/μL for ≥14 days), occurred in 21% of patients. The binary HT score was associated with clinically significant neutropenia (odds ratio [OR], 2. 94; 95% confidence interval [CI], 1. 27-6. 80; P = .

012) with a good predictive performance (area under the curve = 0. 73). Similar results were achieved for early and late ICAHT grade ≥3 (OR, 2. 92; 95% CI, 1. 19-7. 14; P = . 019; and OR, 2. 42; 95% CI, 1. 31-4. 47; P = . 005). A trend toward an association with severe infections was observed (OR, 2. 02; 95% CI, 0. 91-4. 48; P = . 085).

HThigh patients had a lower progression-free and overall survival (hazard ratio [HR], 1. 84; 95% CI, 1. 15-2. 93; P = . 011; and HR, 2. 83; 95% CI, 1. 64-4. 87; P < . 001, respectively). The HT score identified CART-treated patients with R/R LBCL at risk of clinically significant neutropenia, poor survival outcomes, and potentially severe infections.