Impact of corticosteroid and tocilizumab use on infection incidence and outcomes following CAR T-cell therapy with axicabtagene ciloleucel.

Abstract

e19007 Background: Corticosteroids and tocilizumab are frequently used to manage cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) following chimeric antigen receptor T-cell (CAR-T) therapy. However, their impact on post-infusion complications remains uncertain. We aimed to evaluate the association between corticosteroid or tocilizumab exposure and outcomes after CAR-T therapy. Methods: A retrospective multicenter analysis was performed using publicly available data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry (P-6093, Wudhikarn et al.), limited to patients who received axi-cel. Patients receiving corticosteroids and/or tocilizumab following CAR-T infusion were compared against those who did not. The primary outcome was 100-day infection incidence (overall, bacterial, viral, and fungal). Secondary outcomes included overall survival (OS), neutrophil engraftment, and infection-related mortality (IRM). Baseline characteristics were compared using chi-square and t-tests. Associations between corticosteroid/tocilizumab use and outcomes were assessed using Cox proportional hazards models adjusted for age, Karnofsky performance status (KPS), hematopoietic cell transplantation comorbidity index (HCT-CI), disease category, prior HCT, and transformed lymphoma status. Statistical significance was defined as p<0.05. Results: Among 2,749 CAR-T recipients, 1,873 (68.1%) received corticosteroids or tocilizumab. These patients were older (60.2±12.6 vs 58.1±13.4 years; p<0.001), had lower KPS (20.4% vs 15% with KPS < 80; p<0.001), and more frequently had transformed lymphoma (74% vs 64%; p<0.001) compared to those who did not. Corticosteroid/tocilizumab use was independently associated with higher 100-day overall infection incidence (HR 1.64; 95%CI 1.33–2.01; p<0.001), bacterial infections (HR 1.92; 95%CI 1.46–2.52; p<0.001), and fungal infections (HR 2.47; 95%CI 1.25–4.88; p=0.009). Viral infections were not significantly different between the two groups (HR 1.34; 95%CI 0.99–1.80; p=0.057). The use of corticosteroids/tocilizumab was also significantly associated with increased infection-related mortality (HR 4.24; 95%CI 1.29–13.94; p=0.018). However, there was no statistically significant difference in terms of overall survival (HR 1.11; 95%CI 0.96–1.27; p=0.149) or neutrophil engraftment (HR 0.92; 95%CI 0.84–1.01; p=0.089). Conclusions: Corticosteroid and tocilizumab use following CAR-T therapy is independently associated with an increased risk of bacterial and fungal infections and higher infection-related mortality, highlighting the importance of antimicrobial prophylaxis and infection surveillance.