In the phase III TEAMM trial reported in The Lancet Oncology, Drayson et al found that prophylactic treatment with levofloxacin during the first 12 weeks of multiple myeloma treatment in newly diagnosed patients was associated with a significant reduction in first febrile episodes or death from any cause.
Study Details
In the double-blind trial, 977 patients aged ≥ 21 years from 93 sites in the United Kingdom who had started active myeloma treatment within the previous 14 days were randomly assigned between August 2012 and April 2016 to receive levofloxacin at 500 mg (n = 489) or placebo (n = 488) once daily for 12 weeks. Dose was reduced according to estimated glomerular filtration rate every 4 weeks. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment in the intention-to-treat population.
KEY POINTS
- Levofloxacin prophylaxis was associated with a reduction in the primary endpoint of first febrile episodes or death from any cause.
- Use of levofloxacin was not associated with increased incidence of nonfebrile infections.
Benefit of Prophylactic Levofloxacin
First febrile episodes or death occurred in 19% of patients in the levofloxacin group vs 27% of patients in the placebo group during the first 12 weeks of treatment (hazard ratio [HR] = 0.66, P = .0018). Febrile episodes occurred in 18% vs 23% (87 vs 112 patients), death from any cause occurred in 1% vs 3% (4 vs 15 patients), and febrile episodes with death occurred in 1% vs 1% (4 vs 7 patients). Nonfebrile infections requiring anti-infective treatment occurred in 24% of patients in the levofloxacin group vs 27% of the patients in the placebo group (P = .23).
Adverse Events
Serious adverse events were reported in 52% of the levofloxacin group vs 48% of the placebo group in the 16 weeks from the start of myeloma treatment. These were similar in the two groups except for the occurrence of tendonitis (mostly reversible) in five patients in the levofloxacin group.
The investigators concluded, “Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care–associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing antimyeloma therapy.”
Mark T. Drayson, FRCPath, of the School of Immunity and Infection, University of Birmingham, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by UK National Institute for Health Research. For full disclosures of the study authors, visit thelancet.com.
