Levofloxacin for the prevention of febrile episodes in non-Hodgkin lymphoma patients treated with CHOP plus rituximab in a randomized controlled trial

The role of antibacterial prophylaxis in non-Hodgkin lymphoma (NHL) patients undergoing Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisolone (R-CHOP) chemotherapy with granulocyte-colony stimulating factor (G-CSF) support remains uncertain. This study evaluates the efficacy of levofloxacin in preventing febrile episodes in these patients. A randomized, single-blind, placebo-controlled trial was conducted, enrolling NHL patients receiving R-CHOP every 21-day cycle between January 2023 and June 2024. Patients were randomized to receive levofloxacin 500 mg once daily or placebo from day 1 to day 7 post-chemotherapy. All patients received G-CSF support. The primary outcome was the occurrence of febrile episodes within 120 days. Eighty participants were equally randomized into two groups. The median age was 64 years. In the intention-to-treat analysis, the first febrile episode was documented in 3 (7.5%) and 12 (30%) participants in the levofloxacin and placebo groups, respectively (P = 0.010). Levofloxacin prophylaxis significantly reduced febrile neutropenia (2.5% vs. 20%, P = 0.029) and the composite of febrile episodes, septic shock, all-cause mortality and chemotherapy dose reduction (10% vs. 30%, P = 0.025). The hazard ratio (HR) for fever-free survival with levofloxacin prophylaxis was 0.23 (95% CI 0.06-0.80; P = 0.012). Multivariate analysis showed levofloxacin was associated with a lower risk of febrile episodes (adjusted HR 0.17, 95% CI, 0.05-0.66; P = 0.01). No differences in mortality or serious adverse events were observed. Levofloxacin prophylaxis is an effective, well-tolerated strategy to reduce febrile episodes, febrile neutropenia and composite adverse outcomes after R-CHOP chemotherapy, despite concurrent G-CSF support. Long-term antibiotic resistance monitoring is warranted. Trial registration: This trial is registered at Thai Clinical Trials Registry (TCTR), number TCTR20230719005.