Early antibiotic de-escalation and discontinuation in Patients with Febrile Neutropenia after Cellular Therapy: A Single Center Prospective Unblinded Randomized Trial

Abstract Background - The optimal duration and spectrum of empiric antimicrobial therapy of febrile neutropenia in patients after cellular therapy is unclear. Early de-escalation has been suggested by several groups, however studies exclusively focusing on this group of patients are lacking. Methods – we performed a randomized controlled study to evaluate the safety and non-inferiority in terms of infectious and transplantation-associated outcomes in patients after cellular therapy with febrile neutropenia who received either standard broad spectrum antibiotic treatment until recovery of neutropenia (control group) versus early de-escalation and discontinuation (EDD) antibiotic strategy. Results – we randomized 110 patients (control group, n = 51, EDD group, n = 59). The fraction of antibiotic-free neutropenia days was higher for patients in the EDD group compared to control group (median [IQR], 0.8 [0.62–0.86] versus 0.51 [0.17–0.86], respectively, p = .016). This was true for both per-protocol population and for the allogeneic HCT, autologous HCT, and anti-CD19 CAR-T subgroups. Antibiotic success rate, breakthrough fever, death within 30 days, and other common cellular therapy-related toxicities were all similar between the 2 groups. Conclusions – An EDD antibiotic strategy in patients after cellular therapy was safe and associated with a substantial reduction in broad-spectrum antibiotic utilization without compromising cellular therapy outcomes.