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

Boer, J.W. de; Keijzer, K.; Dorp, S. van; Mutsaers, P.G.N.J.; Niezink, A.G.H.; Doesum, J.A. van; Serroukh, Y.I.M.; Muntendam, L.W.; Pulles, A.E.; Kret, E.J.; Sijs-Szabo, A.; Oomen, J.; Demandt, A.M.P.; Stevens, W.B.C.; Kuipers, M.T.; Pennings, E.R.A.; Spanjaart, A.M.; Kersten, M.J.; Jak, M.; Dijk, L.V. van; Poel, M.W.M. van der; Vermaat, J.S.P.; Meerten, T. van; Dutch CAR T Tumorboard Consortium

doi:doi:10.1182/bloodadvances.2025016689

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/mu L for >= 14 days), occurred in 21% of...Show moreEarly 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/mu L 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.Show less

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