Evaluation of Toxicity Grading Systems in CD19 CAR T-Cell Therapy
Gomez-Llobell M, Serrat SE, Bromberg M, et al. Impact of ASTCT Toxicity Grading System on Outcomes After CAR-T for Mature B-Cell Malignancies. Transplantation and Cellular Therapy. 2026; (doi: 10.1016/j.jtct.2026.05.032).
A retrospective study underscores the value of contemporary grading systems for interpreting post–chimeric antigen receptor (CAR) T-cell therapy outcomes. The sample population included 560 adults with mature B-cell malignancies who underwent CD19-targeted CAR T treatment between 2016 and 2024 and were followed for a median of 23.9 months. Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded based on the American Society for Transplantation and Cellular Therapy's (ASTCT) toxicity grading system, while early immune effector cell–associated hematologic toxicity (ICAHT) was classified under European consensus definitions. Researchers documented 140 cases of grade 2 CRS and 61 cases of grades 3–4 CRS; 40 instances of grade 2 ICANS and 74 instances of grades 3–4 ICANS; and 151 cases of grade 2 early ICAHT and 144 cases of grades 3–4 ICAHT. At 2 years, the cumulative incidence of non-relapse mortality (NRM) was 7.2% for the full cohort. Overall survival (OS) and progression-free survival (PFS) were 57% and 41%, respectively. Analysis revealed that acute CRS or early ICAHT status was not independently associated with NRM, OS, or PFS, although severe ICANS was associated with increased NRM and inferior OS. The data support the utility of grading systems such as ASTCT's and identify neurotoxicity as a priority for prophylaxis and management following CD19 CAR-T therapy.