Adding levofloxacin to antimyeloma therapy improved survival and reduced infections in patients with newly diagnosed myeloma, findings from a phase 3 trial suggest.
The advantages of levofloxacin prophylaxis appear to offset the potential risks in patients with newly diagnosed disease, explained, of the University of Birmingham (England) and colleagues. The study was published in the .
The randomized, placebo-controlled, phase 3enrolled 977 patients with newly diagnosed myeloma. The effects of antimicrobial prophylaxis on infection risk and infection-related mortality were evaluated across 93 hospitals throughout the United Kingdom.
Study patients were randomly assigned to receive 500 mg of oral levofloxacin once daily or placebo for a total of 12 weeks. If applicable, dose adjustments were made based on estimated glomerular filtration rate.
At baseline, the team collected stool samples and nasal swabs, and follow-up assessment occurred every 4 weeks for up to 1 year. The primary endpoint was time to death (all causes) or first febrile event from the start of prophylactic therapy to 12 weeks.
After a median follow-up of 12 months, first febrile episodes or deaths were significantly lower for patients in the levofloxacin arm (19%), compared with the placebo arm (27%) for a hazard ratio for time to first event of 0.66 (95% confidence interval, 0.51-0.86; P = .0018).
With respect to safety, the rates of serious adverse events were similar between the study arms, with the exception of tendinitis in the levofloxacin group (1%). Among all patients, a total of 597 serious toxicities were observed from baseline to 16 weeks (52% in the levofloxacin arm vs. 48% in the placebo arm).
“To our knowledge, this is the first time that the use of prophylactic antibiotics has shown a survival benefit in patients with newly diagnosed myeloma,” the researchers reported.
One key limitation of the study was the younger patient population relative to the general population. As a result, differences in survival estimates could exist between the trial and real-world populations, they noted.
“Patients with newly diagnosed myeloma could benefit from levofloxacin prophylaxis, although local antibiotic resistance proportions must be considered,” the researchers cautioned.
The study was funded by the National Institute for Health Research in the United Kingdom. The authors reported financial affiliations with Actelion, Astellas, Celgene, Gilead, Janssen, Pfizer, Takeda, and other companies.
SOURCE: Drayson MT et al. Lancet Oncol. 2019 Oct 23. .