Prospective Validation of CAR-HEMATOTOX and a Simplified Version Predict Survival in Patients with Large B-Cell Lymphoma Treated with Anti-CD19 CAR T-Cells: Data from CART-SIE Study
Federico Stella, Martina Pennisi, Annalisa Chiappella, Beatrice Casadei, Stéfania Bramanti, Silva Ljevar, Patrizia Chiusolo, Alice Di Rocco, Maria Chiara Tisi, Piera Angelillo, Ilaria Cutini, Massimo Martino, Angelica Barone, Francesca Bonifazi, Armando Santoro, Federica Sorà, Mattia Novo, Anna Maria Barbui, Domenico Russo, Maurizio Musso, Giovanni Grillo, Mauro Krampera, Jacopo Olivieri, Lucia Brunello, Federica Cavallo, Massimo Massaia, Luca Arcaini, Lucia Farina, Pier Luigi Zinzani, Rosalba Miceli, Paolo Corradini
Abstract
Anti-CD19 CAR T-cells have revolutionized outcomes in relapsed/refractory large B-cell lymphomas. Long-term follow-up underscored the role of hematological toxicity in nonrelapse mortality, largely driven by infections, leading to the development of the CAR-HEMATOTOX (HT) score for predicting neutropenia. The European scientific community (EHA/EBMT) later reached a consensus, defining a new entity: immune effector cell–associated hematotoxicity (ICAHT). To validate the ability of the HT score to predict ICAHT and survival. The CART-SIE is an ongoing multicenter prospective observational study collecting data on patients affected by B-cell lymphoma treated with commercial anti-CD19 CAR T-cells (ClinicalTrials.gov ID: NCT06339255). Since 2019 to 2024, 1002 consecutive patients were enrolled. Out of 746 patients infused, the HT score at infusion was evaluable in 389. Median age was 59 years (48-66). Patients with high HT score had greater disease burden and a greater need for bridge therapy. Patients with a HT HIGH score had a 4-fold higher risk of experiencing late ICAHT of grade ≥ 3 (OR = 3.99, 95% CI = 1.16-13.77, P = .03). Patients with a HT HIGH score also showed lower overall response rates (ORR) and complete response rates (CRR) at 90 days (CRR at 90 days: 59% HT LOW versus 38% HT HIGH , OR = 0.42, 95% CI = 0.27-0.66, P = .0002; ORR at 90 days: 67% HT LOW versus 49% HT HIGH , OR = 0.47, 95% CI = 0.29-0.74, P = .001). Adjusted logistic models confirmed that the effect of HT score was independent from baseline characteristics. With a median follow-up of 18 months, patients with a HT HIGH score have lower OS and PFS (1-year OS: 78% HT LOW versus 62% HT HIGH , P = .0002; 1-year PFS: 49% versus 39%, P = .003). Adjusted Cox models confirmed that HT was an independent prognostic factor for OS. A high HT-score was found to be associated with higher risk of secondary primary malignancy (HR=2.8, 95% CI = 1.03-7.8, P = .04). A simplified version of HT (simpleHT), based solely on the platelet count and C-reactive protein at infusion, was calculated for 560 patients and proved significant in predicting both OS and PFS (1-year was 72% simpleHT LOW versus 37% simpleHT HIGH , P < .0001, 1-year PFS was 48% simpleHT LOW versus 22% simpleHT HIGH , P < .0001). In our prospective real-world study, we validated the ability of the HT score to predict ICAHT and survival. SimpleHT identified a population at very high risk with an impaired progression free and overall survival.