Infections in the first 30-days after CAR-T therapy in Patients Not Receiving Fluoroquinolone Prophylaxis.

BACKGROUND: Routine fluoroquinolone (FQ) prophylaxis may increase the risk of antimicrobial resistance, microbiome disruption, and Clostridioides difficile infection in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy for haematological malignancy. In Australia, FQ prophylaxis is not routinely used. We evaluated the aetiology of early fever following CAR-T to better understand the incidence of infections, particularly bloodstream infections, in a cohort not receiving FQ prophylaxis. METHODS: This bicentric Australian retrospective study included adults receiving standard-of-care CD19 CAR-T therapy for DLBCL (2019-2023). The primary outcome was the cause of sustained fever (≥38.0°C on ≥1 days) from infusion to day 30. Recurrent fever required ≥72 hours afebrile before a new fever. Infections were classified as microbiologically-confirmed, clinically-defined, or fever syndrome per consensus criteria. RESULTS: 204 adults (median age 64 years, IQR:57-71) received tisagenlecleucel (50%) and axicabtagene (50%), after a median of 3 prior therapies (IQR:3-4). Sustained fever occurred in 131/204 patients (64%), comprising 161 episodes. Of these, 36 (21%, 28pts) were microbiologically-confirmed infections, 14 (9%, 14pts) were clinically-defined infections, and 110 (69%, 108pts) were fevers of unknown origin. Bacteremia occurred in 7/204 patients (3.4%; 9 events), with one fatal polymicrobial bacteremia. Other microbiologically-confirmed infections included C. difficile (7/36), URTI (13/36) and invasive fungal infection (5/36). Risk factors for early microbiologically-confirmed infection in univariate analysis included axicabtagene product (HR=2.5, p=0.019), grade ≥3 ICANS (HR=3.4, p=0.012), and prolonged neutropenia (ANC ≤ 0.5 × 10⁹/L for ≥14 days; HR=3.7, p=0.014). CONCLUSION: Early bacteremia rates remain low without routine FQ prophylaxis. Initial sustained fevers are predominantly non-infectious. Our data do not support universal fluoroquinolone prophylaxis in CAR-T therapy.