Effect of Levofloxacin Prophylaxis on Rates of Febrile Neutropenia in Patients Receiving DA-EPOCH-R Chemotherapy for Aggressive Lymphomas
Authors: Parker Brent Alexander , Dehghani Mina , Lam Selay , Phua Chai Wye , Foster Cheryl , Howson-Jan Kang , Mangel Joy 
Published: November 2021

Abstract
Introduction: Febrile neutropenia (FN) is a serious potential adverse event of myelosuppressive chemotherapy. Dose-adjusted EPOCH-R (DA-EPOCH-R: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab, with doses adjusted to induce neutropenia of &lt; 0.5 x 10 9/L) is a chemoimmunotherapy regimen used for aggressive lymphomas including diffuse large B-cell lymphoma, double/triple hit, Burkitt, primary mediastinal, and HIV-associated large cell lymphoma. It is associated with high rates of FN (13-25% of cycles) despite use of prophylactic Septra and granulocyte colony stimulating factor (G-CSF). Fluoroquinolone antibiotics have been used in various hematological malignancies to reduce infection rates while on chemotherapy, but this strategy has never been reported with DA-EPOCH-R. This study was conducted to assess the impact of adding routine Levofloxacin prophylaxis on FN and infection rates in patients receiving DA-EPOCH-R.
Methods: This is a combined cohort study comparing the patients who received DA-EPOCH-R for newly diagnosed aggressive lymphoma at the London Regional Cancer Program in London, Ontario, Canada before and after the initiation of routine Levofloxacin prophylaxis in July 2020. The prospective cohort received Levofloxacin 500 mg x 7 days with each cycle starting on cycle day 8 in addition to standard supportive care with Septra and G-CSF. The primary objective was the rate of febrile neutropenia. Secondary objectives included days hospitalized, deaths related to infections, and adverse events secondary to Levofloxacin.
Results: Thirty patients who received DA-EPOCH-R in the 5 years preceding the initiation of routine prophylactic Levofloxacin were included in the retrospective cohort. Median age was 58 (range 18-79), 66% were male, and 90% had stage III/IV disease. Total number of cycles of DA-EPOCH-R received was 110, with a median of 4 cycles per patient (range: 1-6). FN developed in 14 patients (46%), and complicated a total of 20 cycles (18%) of DA-EPOCH-R. There were 19 hospital admissions due to FN, with a median duration of hospitalization of 12 days (range 3-120). Two patients died, both due to infection.
Thirteen patients have been treated so far in the prospective cohort, 12 of whom received levofloxacin prophylaxis. Median age was 59 (range 23-69), 66% were male, and 76% had stage III/IV disease. Total number of cycles of DA-EPOCH-R received was 60, with a median of 5 cycles per patient (range: 1-6 ). Only 1 patient (8%) developed FN, which complicated a total of 3 cycles (5%) of chemotherapy. All 3 episodes of FN resulted in hospitalization for a median duration of 30 days (range 20-49). There have been no deaths due to infection in this cohort thus far. No concerning adverse effects from Levofloxacin have been observed.
Conclusions: Although enrollment in the prospective cohort is ongoing, preliminary data are highly encouraging, with significantly lower rates of FN and death due to infection observed since the introduction of routine Levofloxacin prophylaxis. The addition of Levofloxacin to standard prophylaxis with Septra and G-CSF seems to be an effective way to mitigate the risks to patients on DA-EPOCH-R for aggressive lymphomas, and this strategy is worthy of further study.

Disclosures
Lam: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria.