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

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.

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Journal
Blood Advances
Published
2025-07-16
DOI
https://doi.org/10.1182/bloodadvances.2025016689
Citations
2
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
2.09
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article

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

Elise R. A. Pennings, Anne M. Spanjaart, Esther J Kret, Pim G. N. J. Mutsaers et al.
2 citations
Blood Advances
CAR-T cell therapy research
2.09
article

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

Elise R. A. Pennings, Anne M. Spanjaart, Esther J Kret, Pim G. N. J. Mutsaers, Lisanne V. van Dijk, Anikó Sijs‐Szabó, Astrid Demandt, Yasmina Serroukh, Marie José Kersten, Tom van Meerten, Wendy B.C. Stevens, Astrid E. Pulles, Jesse Oomen, Anne G.H. Niezink, Maria T. Kuipers, Joost S.P. Vermaat, Kylie Keijzer, Suzanne van Dorp, Jaap A. van Doesum, Margot Jak, Janneke de Boer, Marjolein WM van der Poel, Louise W. Muntendam
article en
2 citations

Abstract

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.

Blood AdvancesVol. 9(21)
University Medical Center Groningen (NL), Radboud University Nijmegen (NL), University of Groningen (NL), Leiden University Medical Center (NL), Maastricht University Medical Centre (NL), Erasmus MC (NL), Radboud University Medical Center (NL), University Medical Center Utrecht (NL), Maastricht University (NL), Amsterdam Neuroscience (NL), Erasmus MC Cancer Institute (NL), Amsterdam University Medical Centers (NL), International Myeloma Foundation (US), Maastro Clinic (NL), Vrije Universiteit Amsterdam (NL), University of Amsterdam (NL), Erasmus University Rotterdam (NL)
Good health and well-being
Openalex Percentile: Top 11%
CAR-T cell therapy research
2.09
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