1. Inicio
  2. Publicaciones
  3. Impact of ASTCT Toxicity Grading System on Outcomes After CAR-T for Mature B-Cell Malignancies

Impact of ASTCT Toxicity Grading System on Outcomes After CAR-T for Mature B-Cell Malignancies

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Gomez-Llobell M.
  • Escribano Serrat S.
  • Bromberg M.
  • Seshan V.
  • Devlin S.
  • Einarsdottir S.
  • Ben Valid O.
  • Golan-Aceb N.
  • Marcus R.
  • Simoni A.
  • Beyar-Katz O.
  • Perek S.
  • Abed Al Wahad A.
  • Corona M.
  • Rejeski K.
  • Raj S.S.
  • Dahi P.
  • Scordo M.
  • Shah G.L.
  • Palomba M.L.
  • Salles G.
  • Park J.H.
  • Shouval R.
  • Avigdor A.
  • Perales M.-A.

Grupos

Abstract

The American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading system standardized the classification of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) after chimeric antigen receptor (CAR) T-cell therapy. However, the prognostic relevance of CRS and ICANS, as well as immune effector cell-associated hematological toxicity (ICAHT), remains incompletely defined. In this multicenter retrospective study, adult patients with mature B-cell malignancies treated with CD19-directed CAR-T therapy between 2016 and 2024 at three academic centers were included. CRS and ICANS were graded according to ASTCT criteria, and early ICAHT according to EHA/EBMT consensus definitions. The primary endpoint was non-relapse mortality (NRM); secondary endpoints included overall survival (OS) and progression-free survival (PFS). Outcomes were evaluated using day 30 landmark analyses with multivariable models stratified by center and adjusted for clinically relevant covariates; a complementary sensitivity analysis modeled CRS as a time-dependent covariate for NRM in the full cohort from day 0. Among 560 patients, axi-cel was the most frequently used product (48%), followed by tisa-cel (25%), liso-cel (23%) and brexu-cel (4%). With a median follow-up of 23.9 months, the 2-year cumulative incidence of NRM for the full cohort was 7.2%, with 2-year OS and PFS of 57% and 41%, respectively. Overall, 140 patients (25%) and 61 (11%) developed grade 2 and grade 3 to 4 CRS, respectively; 40 (7%) and 74 (13%) developed grade 2 and grade 3 to 4 ICANS, respectively; and 151 (30%) and 144 (29%) developed grade 2 and grade 3 to 4 early ICAHT, respectively. In a day +30 landmark analysis adjusted for baseline covariates, CRS and early ICAHT severity was not independently associated with NRM, OS, or PFS. In contrast, grade =3 ICANS was independently associated with increased NRM (HR: 2.46, 95% CI, 1.00 to 6.04) and inferior OS (HR: 1.79, 95% CI, 1.14 to 2.81), but not with PFS. In the sensitivity analysis, grade 3 to 4 CRS was associated with NRM in univariable but not in multivariable analysis. In this real-world cohort of patients treated with CD19 CAR-T cells, we found that high grade ICANS retained independent prognostic significance for outcomes beyond day 30, whereas CRS and early ICAHT did not; however, severe CRS may still contribute to early treatment-related mortality. These findings support the clinical utility of modern grading systems for outcome interpretation and emphasize neurotoxicity as a priority for preventive interventions after CD19 CAR-T therapy. © 2026 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Datos de la publicación

ISSN/ISSNe:
2666-6375, 2666-6367

Transplantation and Cellular Therapy  ELSEVIER SCIENCE INC

Tipo:
Article
Páginas:
-
PubMed:
42178058
Enlace a otro recurso:
www.scopus.com

Documentos

  • No hay documentos

Métricas

Filiaciones mostrar / ocultar

Keywords

  • CAR T-cell therapy; Cytokine release syndrome (CRS); Immune effector cell-associated hematological toxicity (ICAHT); Immune Effector cell-associated neurotoxicity syndrome (ICANS); Non-relapse mortality; Toxicity grading

Cita

Compartir