Infections in the First 30 Days after Chimeric Antigen Receptor T-Cell Therapy in Patients Not Receiving...

Area of Science:

• Hematology
• Oncology
• Infectious Diseases

Background:

• Routine fluoroquinolone (FQ) prophylaxis in chimeric antigen receptor T-cell (CAR-T) therapy may increase risks of antimicrobial resistance, microbiome disruption, and Clostridioides difficile infection.
• Australian clinical practice does not routinely use FQ prophylaxis for CAR-T therapy.
• Understanding early fever aetiology in CAR-T patients not receiving FQ prophylaxis is crucial for infection risk assessment.

Purpose of the Study:

• To evaluate the causes of early sustained fever following CAR-T therapy in a cohort not receiving fluoroquinolone prophylaxis.
• To determine the incidence of infections, particularly bloodstream infections (bacteremia), in this patient group.
• To assess the necessity of routine fluoroquinolone prophylaxis in CAR-T therapy.

Main Methods:

• A bicentric Australian retrospective study of adults receiving standard-of-care CD19 CAR-T therapy for diffuse large B-cell lymphoma (DLBCL) between 2019-2023.
• Primary outcome: cause of sustained fever (≥38.0°C on ≥1 days) from infusion to day 30 post-CAR-T.
• Infections classified as microbiologically-confirmed, clinically-defined, or fever syndrome per consensus criteria.

Main Results:

• Sustained fever occurred in 64% of 204 patients; 21% were microbiologically-confirmed infections, 9% clinically-defined, and 69% fever of unknown origin.
• Bacteremia occurred in 3.4% of patients (9 events), with one fatal polymicrobial bacteremia.
• Risk factors for microbiologically-confirmed infection included specific CAR-T product (axicabtagene), grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS), and prolonged neutropenia.

Conclusions:

• Early bacteremia rates remain low in patients undergoing CAR-T therapy without routine fluoroquinolone prophylaxis.
• Initial sustained fevers post-CAR-T are predominantly non-infectious in origin.
• The findings do not support the routine use of fluoroquinolone prophylaxis in CAR-T therapy.