7020 Background: Corticosteroids are key to CAR-T toxicity management, but the impact of early dosing remains unclear. Over-treatment may blunt efficacy; under-treatment risks severe neurotoxicity. We evaluated early corticosteroid strategies after anti-CD19 CAR-T for large B-cell lymphoma (LBCL). Methods: Multicenter retrospective cohort across 22 U.S. programs (2019–2024). Adults receiving commercial anti-CD19 CAR-T for LBCL were included. Early steroid strategies: (1) Moderate (≤48 h from first fever or grade 1–2 ICANS; 0.5–1 mg/kg for ≤3 days, taper ≤5 days); (2) High-dose (≥1.5 mg/kg or ≥5 days); (3) None within 48 h. Primary endpoint: 12-month overall survival (OS). Secondary endpoints: grade ≥3 ICANS/CRS (Fine-Gray models), ICU admission, hospital stay (LOS), 6-month relapse, and day-30 response. Multivariable Cox/logistic models adjusted for key clinical covariates and center effects. Sensitivity analyses used inverse-probability weighting and time-dependent exposure. Results: N = 2,186; median age 62. Strategies: Moderate 34 %, High-dose 22 %, None 44 %. Versus None, Moderate dosing reduced grade ≥3 ICANS (sub-hazard ratio sHR 0.62, 95 % CI 0.50–0.78; p < 0.001) with no OS change (adjusted hazard ratio aHR 0.96, 0.84–1.10; p = 0.55). High-dose was linked to worse OS (aHR 1.22, 1.05–1.41) and more early relapse (aHR 1.28, 1.06–1.54) despite similar CRS rates. ICU admission was lower with Moderate vs None (adjusted odds ratio aOR 0.78, 0.64–0.95) and LOS shorter (−1.2 days, 95 % CI −2.0 to −0.4). Findings were consistent across age ≥65 and high-risk groups. Conclusions: A moderate, time-limited early steroid approach after anti-CD19 CAR-T reduced severe ICANS without loss of efficacy, whereas high-dose/prolonged use correlated with poorer survival and earlier relapse. Results support adopting standardized moderate early dosing and avoiding routine high-dose regimens. Clinical outcomes by early corticosteroid strategy after anti-CD19 CAR-T. Outcome None (n=963) Moderate (n=742) High-dose (n=481) Adjusted effect vs None (95 % CI) P value 12-mo OS (%) 61 62 55 aHR 0.96 (0.84–1.10); 1.22 (1.05–1.41) 0.55; 0.009 Grade ≥3 ICANS (%) 13.4 8.7 12.9 sHR 0.62 (0.50–0.78); 0.96 (0.75–1.23) <0.001; 0.77 Grade ≥3 CRS (%) 6.1 5.4 5.8 sHR 0.89 (0.67–1.19); 0.94 (0.72–1.23) 0.43; 0.65 ICU admission (%) 18.9 15.4 19.6 aOR 0.78 (0.64–0.95); 1.03 (0.83–1.29) 0.013; 0.77 Hospital LOS (days) 10.1 8.9 10.6 Δ –1.2 (–2.0 to –0.4); Δ +0.3 (–0.5 to +1.1) 0.003; 0.48 Early relapse (6 mo %) 23.7 24.1 29.8 aHR 1.01 (0.87–1.18); 1.28 (1.06–1.54) 0.88; 0.009 Day-30 response (%) 68.2 69.5 66.9 aOR 1.05 (0.90–1.22); 0.94 (0.79–1.12) 0.54; 0.49 Abbreviations: aHR = adjusted hazard ratio; sHR = sub-hazard ratio; aOR = adjusted odds ratio; Δ = adjusted difference in medians.
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