| Description: |
Corticosteroids are commonly used to manage cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) following chimeric antigen receptor (CAR) T‐cell therapy, and yet, their dose‐specific impact on outcomes remains uncertain. We retrospectively evaluated 276 adults with large B‐cell lymphoma (LBCL) treated with CD19‐directed CAR‐T therapy (axi‐cel, tisa‐cel, or liso‐cel) between 2016 and 2023 at a single institution. Cumulative corticosteroid dose was defined as the total dose administered within 21 days of infusion. Corticosteroids were administered to 105 patients (38%), initiated at a median of 5 days post‐infusion (interquartile range [IQR] 3–7) for CRS (38%), ICANS (15%), or both (47%). Use was more frequent with axi‐cel (P < 0.001), although the cumulative dose and duration were similar across products. To assess the impact of corticosteroid exposure, we carried out a 21‐day landmark analysis. Corticosteroid exposure, modeled as a time‐dependent covariate, was not significantly associated with infection risk, non‐relapse mortality, or inferior overall survival (OS) or progression‐free survival (PFS). However, in a landmark analysis, patients receiving above‐median cumulative corticosteroid doses had a significantly higher risk of infection compared to those receiving below‐median corticosteroid doses or no corticosteroids (P = 0.042). In a landmark multivariable analysis, corticosteroid cumulative dose was associated with increased late hematologic toxicity (adjusted hazard ratio [HR] 1.02, 95% CI 1.02–1.03). Finally, in a sensitivity analysis excluding patients with Grade ≥4 CRS/ICANS, corticosteroid cumulative dose remained unassociated with OS or relapse, but was linked to shorter PFS (adjusted HR 1.04, 95% CI 1.01–1.06). These findings support the safe yet judicious use of corticosteroids to manage CAR‐T toxicities in LBCL. |