| Title: |
Systemic inflammation and CAR-T specific toxicities as major drivers of non-relapse mortality: analysis from the Italian prospective observational CART-SIE Study |
| Authors: |
Barone, Angelica; Stella, Federico; Ljevar, Silva; Casadei, Beatrice; Bramanti, Stefania; Chiusolo, Patrizia; Rocco, Alice Di; Tisi, Maria Chiara; Cutini, Ilaria; Angelillo, Piera; Martino, Massimo; Musso, Maurizio; Farina, Mirko; Pennisi, Martina; Barbui, Anna Maria; Freilone, Roberto; Olivieri, Jacopo; Grillo, Giovanni; Musto, Pellegrino; Saraceni, Francesco; Krampera, Mauro; Brunello, Lucia; Castellino, Alessia; Ragaini, Simone; Arcaini, Luca; Chiappella, Annalisa; Guidetti, Anna; Dodero, Anna; Miceli, Rosalba; Zinzani, Pierluigi; Corradini, Paolo |
| Contributors: |
A. Barone; F. Stella; S. Ljevar; B. Casadei; S. Bramanti; P. Chiusolo; A.D. Rocco; M.C. Tisi; I. Cutini; P. Angelillo; M. Martino; M. Musso; M. Farina; M. Pennisi; A.M. Barbui; R. Freilone; J. Olivieri; G. Grillo; P. Musto; F. Saraceni; M. Krampera; L. Brunello; A. Castellino; S. Ragaini; L. Arcaini; A. Chiappella; A. Guidetti; A. Dodero; R. Miceli; P. Zinzani; P. Corradini |
| Publisher Information: |
Elsevier |
| Publication Year: |
2026 |
| Collection: |
The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| Subject Terms: |
Settore MEDS-09/B - Malattie del sangue |
| Description: |
Background: Chimeric antigen receptor (CAR)-T cell therapy has revolutionized outcomes in relapsed/refractory lymphomas, yet non-relapse mortality (NRM) has emerged as a notable concern, with older age and infections identified as major determinants of NRM in real-life studies. Objective: The aim of the present study was to describe the rate and causes of NRM after CAR-T cells and identify risk factors. Study design: Within the framework of the prospective, multicenter, observational CART‐SIE study, we analyzed causes and determinants of NRM in a large real-world cohort of lymphoma patients receiving CAR‐T cells from 2019 to 2025. Associations between NRM and clinical or biological factors were assessed using Fine and Gray subdistribution hazard models. Results: From 2019 to 2025, 1132 patients were enrolled in the CART-SIE Study; among those, 932 were evaluable for outcomes, with a median follow-up of 17.8 months (IQR 6.3-25.4). In this cohort, 305 deaths were observed, mainly occurring after disease progression (n=258); overall, 47 deaths were solely attributable to NRM (5%), either early (≤28 days, 40.4%), late (29-90 days, 23.4%) or very late (>90 days, 36.2%). The 1- and 2-year cumulative incidence of NRM were 5.5% and 8.8%. Infections were the leading cause (51%), followed by CAR-T acute toxicities (CRS, ICANS, and HLH/MAS; 30%), and secondary malignancies (11%). In univariable analysis, age > 60 years, diabetes, atrial fibrillation, high CAR-HEMATOTOX score, elevated ferritin, baseline cytopenias, CRS grade ≥3, any-grade or grade ≥3 ICANS and infectious events were risk factors for NRM. Multivariable models revealed that, among pre-infusion factors, only high ferritin levels (HR 3.23, 95%CI 1.37-7.62, p=0.007) and diabetes (HR 3.93, 95%CI 1.28-12.1, p=0.017) independently predicted NRM, while only severe CRS, ICANS, and infections remained strong post-infusion predictors. Conclusions: These findings emphasize the role of host-related factors and inflammation in shaping CAR-T outcomes. Optimised ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41740850; journal:TRANSPLANTATION AND CELLULAR THERAPY; https://hdl.handle.net/2434/1226061 |
| DOI: |
10.1016/j.jtct.2026.02.048 |
| Availability: |
https://hdl.handle.net/2434/1226061; https://doi.org/10.1016/j.jtct.2026.02.048 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.38346180 |
| Database: |
BASE |