Infections in Patients With Cytokine Release Syndrome/Immune Effector Cell-Associated Neurotoxicity Syndrome...

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common toxicities after chimeric antigen receptor (CAR) T-cell therapy. We evaluated the incidence, timing, microbiology, and risk factors of microbiologically documented infections during the CRS and/or ICANS phase.

Consecutive adults receiving CAR T-cell therapy between 2020 and 2023 were retrospectively analyzed. Infections were classified by type and timing. The 60-day cumulative incidence of first infection and associated factors were assessed using Fine-Gray competing-risk models.

Among 152 CAR T-cell infusions, CRS and/or ICANS occurred in 117 (77.0%) episodes, and 70 (59.8%) required immunomodulatory therapy. An infectious etiology was documented in 30 (25.6%) episodes, yielding 45 documented infections (21 bacterial [46.7%], 17 viral [37.8%], and 7 fungal [15.6%]), more frequent in immunomodulatory-treated episodes (32.9% vs 14.9%; P = .033). At infection onset, median temperature, and C-reactive protein (CRP) levels were lower than at CRS/ICANS diagnosis (37.2°C vs 38.4°C; P < .001 and 3.9 vs 6.0 mg/L; P = .002). In immunomodulatory-treated episodes, median time to first infection was 15 (7-22) days from CRS and 9 (5-20) days from ICANS. The 60-day cumulative infection incidence was 60.0% with multimodal immunosuppression and 20.8% without; multimodal immunosuppression independently increased infection risk (subdistribution hazard ratio [sHR] 3.29; 95% CI 1.38-7.82; P = .007).

The CRS/ICANS phase carries a high risk of bacterial, viral, and fungal infections, particularly under multimodal immunosuppression, while fever and CRP are unreliable indicators. Focused strategies for early detection, prevention, and prompt treatment of infections are urgently needed.