Infections after anti-CD19 chimeric antigen receptor T-cell therapy for hematologic malignancies: timeline, prevention, and uncertainties.

Abstract

Data on the infectious complications of anti-CD19 chimeric antigen receptor-modified T-cell (CAR-T-cell) therapies are scant. The approaches to preventing and managing infections among CAR-T-cell recipients are extrapolated from those of patients with other hematological malignancies. Understanding the incidence and risk factors of infections in these patients will improve clinical outcomes. Infections occur in 23-42% of CAR-T-cell recipients and are most frequent in the first month after infusion, declining sharply thereafter. Risk factors include preinfusion (e.g., prior hematopoietic cell transplant, underlying malignancy) and postinfusion variables (e.g., cytokine release syndrome [CRS], neutropenia). Neutropenic fever after CAR-T-cell therapy is nearly universal but is confounded by CRS. The timeline of infections can be divided into preinfusion (because of the preparative regimen); 0-30 days after infusion, when bacterial infections predominate; and 30 days onwards, when respiratory viral infections predominate. Fungal and herpesviridae infections are uncommon. Recent studies have shed light on the epidemiology of infections after CAR-T-cell therapy. Future efforts should focus on identifying modifiable risk factors for infection, defining neutropenic fever in the setting of CRS, determining the benefit of antimold prophylaxis, and identifying the optimal approach to viral monitoring, vaccination, and immunoglobulin replacement.